CYP2C19 p.Leu391=
c.1173C>A · rs935030527 · VCV747762
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00667%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.37 | GERP 0.82 |
| Overall | ||
| CADD | 0.256 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00667%
Admixed American · 4/59,946 alleles
Filtering AF
0.00226%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00135%
Overall
0.00031%
5/1,613,638 alleles · very rare
exomes 3/1,461,502 · genomes 2/152,136 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00667% | 14,987 |
| South Asian | 0.0011% | 91,074 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- CYP2C19
- Protein
- p.Leu391=
- Coding
- c.1173C>A
- MANE Select
- NM_000769
- dbSNP
- rs935030527
- Type
- single nucleotide variant
- Location
- chr10:94849940 (GRCh38)
- Gene constraint
- LOEUF 1.668 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.24 · 1 PDB
- Residue 391
- an α-helix
Similar variants
- CYP2C19 p.Gly417= Benign ★★ same type
- CYP2C19 p.His353= Benign/Likely benign ★★ same type
- CYP2C19 p.Arg144Ser Uncertain significance ★ same type
- CYP2C19 p.Asn133Lys Uncertain significance ★ ⚠ same type
- CYP2C19 p.Asn418Asp Uncertain significance ★ ⚠ same type
- CYP2C19 p.Asp243Val Uncertain significance ★ ⚠ same type
- CYP2C19 p.Asp408Asn Uncertain significance ★ ⚠ same type
- CYP2C19 p.Asp414His Uncertain significance ★ ⚠ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cyp2c19-p-leu391 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown