Is CYP2C19 p.His396Gln (c.1188T>A) pathogenic?

CYP2C19 p.His396Gln (c.1188T>A) is classified Uncertain significance in CYP2C19 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-12). AlphaMissense: likely benign (0.2413); Absent from gnomAD v4.1.

How common is CYP2C19 p.His396Gln (c.1188T>A) in the general population?

CYP2C19 p.His396Gln (c.1188T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CYP2C19 p.His396Gln (c.1188T>A)?

AlphaMissense predicts likely benign (score 0.2413) — an in-silico prediction, not a clinical call.

CYP2C19 p.His396Gln

c.1188T>A · rs2492894300 · VCV2283328

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2413 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2413	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -6.80	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.96 · evaluated, not missing
Constraint at this position
Conservation	phyloP -15	GERP -7.3
Regional constraint	o/e 1.26	unconstrained · MANE · 90 kb · p 1.3e-10 · regional, not allelic
Overall
CADD	10.55	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CYP2C19
Protein: p.His396Gln
Coding: c.1188T>A
MANE Select: NM_000769
dbSNP: rs2492894300
Type: single nucleotide variant
Location: chr10:94849955 (GRCh38)
Gene constraint: LOEUF 1.668 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.24 · 1 PDB

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

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-his396gln (accessed [today's date]).

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