Is CYP2C19 p.Gly417= (c.1251A>C) pathogenic?

CYP2C19 p.Gly417= (c.1251A>C) is classified Benign in CYP2C19 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-02-24). Common (popmax 8.88%, eas) — too common for a highly-penetrant pathogenic allele.

CYP2C19 p.Gly417=

Q: How common is CYP2C19 p.Gly417= (c.1251A>C) in the general population?

CYP2C19 p.Gly417= (c.1251A>C) is common (popmax 8.88%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1251A>C · rs17886522 · VCV1276601

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 8.88%, eas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP -11	GERP 2.1
Overall
CADD	1.471	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.88% East Asian · 3,983/44,838 alleles

Filtering AF 8.65% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.56%

Overall 0.406% 6,549/1,613,662 alleles · common exomes 5,276/1,461,426 · genomes 1,273/152,236 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	8.88%	11
African / African-American	2.2%	45
Remaining individualsnot grpmax-eligible	0.576%	174
South Asian	0.361%	277
Middle Eastern	0.215%	466
Admixed American	0.0984%	1,016
European (non-Finnish)	0.0125%	7,971
Finnishnot grpmax-eligible	0.0109%	9,148

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.Gly417=
Coding: c.1251A>C
MANE Select: NM_000769
dbSNP: rs17886522
Type: single nucleotide variant
Location: chr10:94850018 (GRCh38)
Gene constraint: LOEUF 1.668 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.24 · 1 PDB
Residue 417: a β-strand

Full CYP2C19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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
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-gly417 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown