Is YAP1 p.Arg331Trp (c.991C>T) pathogenic?

YAP1 p.Arg331Trp (c.991C>T) is classified Likely benign in YAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-01). AlphaMissense: likely pathogenic (0.7668); Ultra-rare (popmax 0.0969%, eas).

How common is YAP1 p.Arg331Trp (c.991C>T) in the general population?

YAP1 p.Arg331Trp (c.991C>T) is ultra-rare (popmax 0.0969%, eas) (gnomAD).

What do computational predictors say about YAP1 p.Arg331Trp (c.991C>T)?

AlphaMissense predicts likely pathogenic (score 0.7668) — an in-silico prediction, not a clinical call.

YAP1 p.Arg331Trp

c.991C>T · rs193100333 · VCV717444

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7668 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0969%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7668	likely pathogenic
REVEL	0.266	benign-leaning
SaProt	LLR -9.25	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 119 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0969% East Asian · 43/44,394 alleles

Filtering AF 0.0739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0657%

Overall 0.0191% 306/1,603,500 alleles · ultra-rare exomes 288/1,452,494 · genomes 18/151,006 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0969%	1,032
Remaining individualsnot grpmax-eligible	0.0451%	2,218
European (non-Finnish)	0.0188%	5,323
Finnishnot grpmax-eligible	0.00948%	10,548
Admixed American	0.00518%	19,323
South Asian	0.00336%	29,760
African / African-American	0.00271%	36,879

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: YAP1
Protein: p.Arg331Trp
Coding: c.991C>T
MANE Select: NM_001130145
dbSNP: rs193100333
Type: single nucleotide variant
Location: chr11:102209523 (GRCh38)
Gene constraint: LOEUF 0.212 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 58.46 · 41 PDB
Residue 331: 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-arg331trp (accessed [today's date]).

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