CYP2C19 p.His353=
c.1059C>T · rs17882744 · VCV2640706
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.39%, afr)
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 -20 | GERP -11 |
| Overall | ||
| CADD | 0.101 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.39%
African / African-American · 1,040/75,028 alleles
Filtering AF
1.32%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.29%
Overall
0.252%
4,074/1,614,166 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.39% | 72 |
| Ashkenazi Jewishnot grpmax-eligible | 0.385% | 260 |
| Remaining individualsnot grpmax-eligible | 0.242% | 414 |
| European (non-Finnish) | 0.22% | 455 |
| Admixed American | 0.178% | 561 |
| Middle Eastern | 0.0825% | 1,212 |
| South Asian | 0.0516% | 1,938 |
| East Asian | 0.0156% | 6,412 |
| Finnishnot grpmax-eligible | 0.0141% | 7,114 |
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.His353=
- Coding
- c.1059C>T
- MANE Select
- NM_000769
- dbSNP
- rs17882744
- Type
- single nucleotide variant
- Location
- chr10:94842934 (GRCh38)
- Gene constraint
- LOEUF 1.668 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.24 · 1 PDB
- Residue 353
- an α-helix
Similar variants
- CYP2C19 p.Gly417= 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
- CYP2C19 p.Asp46Gly 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-his353 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown