Pharmacogenetic Testing

VCF Pharmacogenetics: Turn Any VCF File Into a Pharmacogenetic Report

A VCF is the richest pharmacogenetic data source available, but it comes with no interpretation. Here is how Gene2Rx turns any VCF into a guideline-based report on 110 medications, and what the file still cannot resolve.

Reviewed by the Gene2Rx team · Updated 2026-05-27

A VCF file (Variant Call Format) is the standard output of whole genome sequencing: a list of every position where your DNA differs from the reference, with your full sequence behind it. What a VCF is not is a drug report. That is what Gene2Rx adds. Upload your VCF, from any source, and Gene2Rx turns it into a pharmacogenetics report covering 110 medications, built on the same CPIC[1] and FDA[2] guidelines clinicians use. It runs in minutes, costs $5 for a starter report or $49 for the full report, plus a $15 surcharge for WGS and VCF uploads because they take more processing (so a full VCF report is $64), needs no doctor's order, and never expires, because your DNA does not change.

Important: A pharmacogenetic report from your VCF data is informational and does not replace medical advice. Never change or stop a medication based on genetic results alone. Always discuss the report with your healthcare provider before making any treatment change.

$64 a full 110-medication report from a VCF you already have: the $49 report plus the $15 sequencing surcharge

What a VCF gives you, and what it leaves out

Any VCF works, regardless of where it came from

Gene2Rx accepts VCF files from any WGS provider (Nebula, Dante Labs, Sequencing.com, Nucleus, Veritas), from research studies, and from clinical sequencing labs. The format is standardized, so the pipeline does not care which lab produced the file. Plain .vcf and bgzip-compressed .vcf.gz are both accepted, and you do not need to filter or subset the file first; Gene2Rx extracts only the pharmacogenetic variants it needs.

GRCh37 and GRCh38 are both auto-detected

Every VCF specifies which reference genome build its positions are called against. GRCh37 and GRCh38 are the two common builds, and Gene2Rx handles both. You do not need to lift over the file to a specific build before uploading. The pipeline auto-detects the build from the VCF header or infers it from variant positions, then maps the pharmacogenetic loci correctly regardless of which build your VCF uses.

What Gene2Rx produces from your VCF

Gene2Rx reads your VCF, calls your metabolizer phenotype for each pharmacogene (poor, intermediate, normal, rapid, or ultrarapid), and maps each phenotype to specific recommendations for 110 medications, with every recommendation traceable to its CPIC or FDA guideline. The report spans psychiatry, cardiology, pain, chemotherapy, transplant, and gastrointestinal drugs. It is delivered in minutes, with no new sample and no prescriber required.

WGS depth resolves the variants chips miss, and the file lasts for life

A WGS VCF reads every base, so it can contain rare loss-of-function variants in genes like DPYD,[8] TPMT,[9] CYP2C19,[5] and CYP2D6[3] that a genotyping chip was never designed to detect. That is the real data-quality edge of starting from a VCF. One limit to know: Gene2Rx works from the variant calls in your VCF, so it does not detect copy-number changes such as CYP2D6 gene duplications or deletions, which require raw alignment files. And because the file already contains every position in your genome, you can re-run it against the same analysis as CPIC and FDA guidelines evolve, with no new lab work. A Gene2Rx report is $5 for the starter tier or $49 for the full report, plus the $15 surcharge, and your pharmacogenetic profile never changes, so one VCF is a reference you will use for decades.

Because the file already contains every position in your genome, you can re-run it against updated guidelines with no new lab work.

How your genetics can play a role

These are the main genes Gene2Rx reads out of your VCF and what each one affects. The biology is the same no matter which data source you start from; what a VCF provides is the raw genotype at these positions.

GeneWhat it affects
CYP2D6 Metabolizes many antidepressants (paroxetine, venlafaxine, fluoxetine, amitriptyline), the ADHD drug atomoxetine, several antipsychotics, tamoxifen, and the opioids codeine and tramadol.[3] About 5 to 10 percent of people are poor metabolizers, varying by ancestry. For poor metabolizers, codeine and tramadol give little pain relief; ultrarapid metabolizers can reach unsafe opioid levels at standard doses. A whole genome VCF includes rarer CYP2D6 variants that a genotyping chip does not probe, but Gene2Rx does not call CYP2D6 copy-number changes (duplications or deletions) from a VCF; that requires raw alignment data.
CYP2C19 Affects SSRIs (sertraline, citalopram, escitalopram[4]), the antiplatelet clopidogrel,[5] and proton pump inhibitors (omeprazole). Poor metabolizers get inadequate platelet protection from clopidogrel; rapid and ultrarapid metabolizers can clear SSRIs and PPIs too fast for standard doses to work.
CYP2C9 and VKORC1 Together these drive warfarin dosing.[6] If you ever need this blood thinner, your CYP2C9 and VKORC1 genotypes help predict the right starting dose and avoid dangerous over- or under-anticoagulation. CYP2C9 also affects some NSAIDs and phenytoin.
SLCO1B1 Sets your risk of statin-associated muscle pain.[7] About 15 to 20 percent of people carry a decreased-function variant, most relevant for simvastatin. The usual fix is switching within the statin class, not stopping statins.
DPYD Determines safety of the fluoropyrimidine chemotherapy drugs capecitabine and fluorouracil.[8] Reduced-function carriers can suffer severe, occasionally fatal toxicity at standard doses, so knowing your status before chemotherapy is genuinely high-stakes.
TPMT and NUDT15 Guide dosing of thiopurine drugs (azathioprine, mercaptopurine) used in autoimmune disease and leukemia.[9] Poor metabolizers risk severe bone marrow suppression at standard doses and need a substantially reduced dose.
HLA-B (not reported by Gene2Rx) HLA-B*57:01 (abacavir) and HLA-B*15:02 (carbamazepine in at-risk populations) are immune-mediated hypersensitivity markers that WGS resolves well. Gene2Rx does not currently report HLA alleles, however; HLA typing is offered as a separate clinical test.

Your VCF contains the genotypes for all of these genes; the only thing standing between that and actionable guidance is interpretation. Gene2Rx translates your genotypes into metabolizer phenotypes for each gene, then maps those phenotypes to specific medication recommendations anchored to CPIC[1] and FDA[2] guidelines, so the output reads the same way a clinical pharmacogenetic report would. Because a WGS VCF observes more of the underlying variation directly, confidence in each phenotype assignment is typically higher than for genotyping-based reports.

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When to consider pharmacogenetic testing

If you have a VCF from any source (consumer service, research study, or clinical sequencing), running a pharmacogenetic analysis is one of the highest-value uses of that data, and the starter report is $5 plus the $15 VCF surcharge. It is most valuable if you are starting or already taking a medication with pharmacogenetic guidelines, if you have had side effects or poor response in the past, or if you are preparing for chemotherapy. Because your genotype never changes, one report serves you for life, and you can re-run the same VCF as guidelines evolve.

What you can do next

  1. Locate your VCF file. Most WGS providers deliver it through their member portal or as part of your raw data package; research and clinical sources provide it on request.
  2. Upload the file to gene2rx.com. Both .vcf and compressed .vcf.gz are accepted, and both GRCh37 and GRCh38 builds are supported and auto-detected. The starter report is $5 and the full 110-medication report is $49, each plus a $15 surcharge for WGS and VCF uploads because they take more processing.
  3. Review your metabolizer status for each pharmacogene and the medications flagged for you.
  4. Save the report and share the relevant section with your doctor or pharmacist before any new prescription.

See how genetics may affect your response to Sertraline, Sertraline, Escitalopram, Clopidogrel, Warfarin, Capecitabine, Codeine, Tramadol, Tacrolimus.

Frequently asked questions

What VCF formats does Gene2Rx accept?

Plain .vcf and bgzip-compressed .vcf.gz files, from any source. Both GRCh37 and GRCh38 reference genomes are supported; the pipeline auto-detects the build and maps pharmacogenetic loci correctly regardless.

Do I need to pre-process or filter the VCF?

No. Upload the raw VCF as delivered. The Gene2Rx pipeline extracts only the variants it needs for pharmacogenetic interpretation, so you do not need to subset the file.

What sequencing depth is sufficient?

30x whole genome coverage (the standard for most consumer WGS services) is more than enough for reliable pharmacogenetic interpretation. Lower coverage can work but confidence on rare variants decreases. Exome-only VCFs work for most pharmacogenes but may miss some regulatory and intronic positions; coverage varies by exome capture kit.

Can I use a VCF from a research study or clinical sequencing?

Yes. Gene2Rx accepts VCFs from any source. The format is standardized, so the pipeline does not care which lab produced it. Upload it for $5 (starter) or $49 (full), plus the $15 VCF surcharge.

How is pharmacogenetic analysis from a VCF different from 23andMe-based analysis?

The clinical guidelines are the same (CPIC, FDA). The difference is data quality. A WGS VCF contains far more of your variants, so rare alleles a chip never probed are available to the analysis. Consumer genotyping arrays (23andMe, AncestryDNA) cover only the variants they were designed to detect. For most people, consumer-array pharmacogenetics works well; for patients with non-European ancestry or rare variants, a VCF is meaningfully better. Note that copy-number changes such as CYP2D6 gene duplications are not called from a VCF; that requires raw alignment data Gene2Rx does not process.

References

  1. Clinical Pharmacogenetics Implementation Consortium (CPIC). CPIC Guidelines. cpicpgx.org
  2. U.S. Food and Drug Administration. Table of Pharmacogenomic Biomarkers in Drug Labeling (2024). fda.gov
  3. CPIC. CPIC Guideline for Opioids (Codeine, Tramadol) and CYP2D6, OPRM1, and COMT (2021). cpicpgx.org
  4. CPIC. CPIC Guideline for SSRI and SNRI Antidepressants and CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A (2023). cpicpgx.org
  5. CPIC. CPIC Guideline for Clopidogrel and CYP2C19 (2022). cpicpgx.org
  6. CPIC. CPIC Guideline for Pharmacogenetics-Guided Warfarin Dosing (CYP2C9, VKORC1, CYP4F2) (2017). cpicpgx.org
  7. CPIC. CPIC Guideline for Statins and SLCO1B1, ABCG2, and CYP2C9 (2022). cpicpgx.org
  8. CPIC. CPIC Guideline for Fluoropyrimidines and DPYD (2017). cpicpgx.org
  9. CPIC. CPIC Guideline for Thiopurines and TPMT and NUDT15 (2018). cpicpgx.org

Disclaimer: This content is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always consult your healthcare provider before making changes to your medication. Never stop or change a medication without medical supervision.

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