CYP2C19 (Cytochrome P450 2C19) variants and mutations

CYP2C19 (also known as Cytochrome P450 2C19) is a human protein-coding gene encoding a cytochrome P450 2C19 protein. It metabolizes many proton-pump inhibitors, antidepressants, and other drugs and is required for efficient activation of clopidogrel. Common alleles produce poor through ultrarapid metabolizer phenotypes that can substantially alter treatment efficacy and toxicity. This analysis covers 1,098 CYP2C19 variants and mutations. Of these, 22% have clinical classifications, 90% have computational variant effect predictions from REVEL and MutPred, 99% have experimental measurements including CYP2C19 VAMP-seq synonymous scores and CYP2C19 VAMP-seq nonsynonymous scores, and 71% have population-specific frequency data. Disease context includes response to clopidogrel and acute coronary syndrome. Example CYP2C19 variants include M1V, D2H, and D2Y.

Variant analysis overview

Gene: CYP2C19
Protein: Cytochrome P450 2C19
UniProt accession: P33261
Organism: Homo sapiens
Variants analyzed: 1098
Variant scope: all variants
Completed: 2026-08-10

Variant and mutation evidence

Variant composition: 839 unspecified-consequence records; 125 missense variants; 100 synonymous variants; 4 stop-gained variants; 21 frameshift variants; 1 in-frame insertions; 5 splice-region variants; 2 in-frame deletions; 1 substitution
Clinical classifications: 20 benign or likely benign; 40 uncertain-significance; 178 other clinical labels.
Computational signals: 17 REVEL high-risk; 3 MutPred high-risk.
Variant classes: 935 missense; 100 synonymous; 60 truncating or splice.
Prediction scores: 989 variants have prediction scores (90% of the analyzed set).
Literature: 9 publications are represented in the literature summary.

Clinical, disease, and population context

Clinical evidence: 26 records have expert-only or criteria-backed evidence.
Clinical annotations: 239 variants have clinical annotations.
Population evidence: 869 variants have population-frequency evidence.
Disease context: 25 disease associations are represented. Top associations: response to clopidogrel, acute coronary syndrome.

Protein structure and variant hotspots

Protein features: 1 binding sites.
Ancestry evidence: 778 variants have ancestry-specific frequency data.
Experimental measurements: 1,086 variants have experimental measurements or scores.
3D hotspots: 1 hotspot clusters were identified. Clusters at residues 171-299 (tolerant, 24 variants).
Allosteric analysis: 1 functional sites were identified.
Experimental data: 487 protein positions have experimental scores. Source: CYP2C19 VAMP-seq synonymous scores, CYP2C19 VAMP-seq nonsynonymous scores.
gnomAD gene constraint: pLI 0.00 (tolerant of loss-of-function variation); LOEUF 1.44; missense Z-score -2.74.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.

Notable CYP2C19 variants

Examples include M1V, D2H, D2Y, D2V, D2E, P3H, P3L, P3S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

CYP2C19 analysis run — CYP2C19 (1,098 variants) — completed 2026-08-10