Is CYP2C19 p.Asp243Val (c.728A>T) pathogenic?

CYP2C19 p.Asp243Val (c.728A>T) is classified Uncertain significance in CYP2C19 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-23). AlphaMissense: likely benign (0.1086); Very rare (popmax 0.000175%, nfe).

How common is CYP2C19 p.Asp243Val (c.728A>T) in the general population?

CYP2C19 p.Asp243Val (c.728A>T) is very rare (popmax 0.000175%, nfe) (gnomAD).

What do computational predictors say about CYP2C19 p.Asp243Val (c.728A>T)?

AlphaMissense predicts likely benign (score 0.1086) — an in-silico prediction, not a clinical call.

CYP2C19 p.Asp243Val

c.728A>T · VCV4658069

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1086 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000175%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1086	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -4.20	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.9	GERP 0.41
Regional constraint	o/e 1.26	unconstrained · MANE · 90 kb · p 1.3e-10 · regional, not allelic
Overall
CADD	7.264	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

Grpmax group 0.000175% European (non-Finnish) · 2/1,139,768 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000148% 2/1,353,534 alleles · very rare

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.Asp243Val
Coding: c.728A>T
MANE Select: NM_000769
Type: single nucleotide variant
Location: chr10:94781906 (GRCh38)
Gene constraint: LOEUF 1.668 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.24 · 1 PDB
Residue 243: an α-helix

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.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-asp243val (accessed [today's date]).

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