Is YAP1 p.Met295Val (c.883A>G) pathogenic?

YAP1 p.Met295Val (c.883A>G) is classified Uncertain significance in YAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-19). AlphaMissense: likely benign (0.0851); Absent from gnomAD v4.1.

How common is YAP1 p.Met295Val (c.883A>G) in the general population?

YAP1 p.Met295Val (c.883A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about YAP1 p.Met295Val (c.883A>G)?

AlphaMissense predicts likely benign (score 0.0851) — an in-silico prediction, not a clinical call.

YAP1 p.Met295Val

c.883A>G · VCV4203038

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0851 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0851	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -6.40	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 -0.57	GERP -4.4
Regional constraint	o/e 0.81	unconstrained · MANE · 119 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	10.11	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: YAP1
Protein: p.Met295Val
Coding: c.883A>G
MANE Select: NM_001130145
Type: single nucleotide variant
Location: chr11:102205973 (GRCh38)
Gene constraint: LOEUF 0.212 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 58.46 · 41 PDB
Residue 295: the 'disordered' region; the 'transactivation domain' region

Full YAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

YAP1 p.Gln238Ter Uncertain significance ★★ same type
YAP1 p.Ser105Pro Uncertain significance ★★ ⚠ same type
YAP1 p.Thr145Ser Uncertain significance ★★ ⚠ same type
YAP1 p.Val55Leu Uncertain significance ★★ ⚠ same type
YAP1 c.1276+42G>C Benign ★★ same type
YAP1 c.322-157A>G Benign ★★ same type
YAP1 c.322-247C>T Benign ★★ same type
YAP1 c.802+206C>A Benign ★★ 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/yap1-p-met295val (accessed [today's date]).

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