Is YAP1 p.Thr255Ser (c.763A>T) pathogenic?

YAP1 p.Thr255Ser (c.763A>T) is classified Uncertain significance in YAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-06). AlphaMissense: ambiguous (0.4044); Very rare (popmax 0.00017%, nfe).

How common is YAP1 p.Thr255Ser (c.763A>T) in the general population?

YAP1 p.Thr255Ser (c.763A>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about YAP1 p.Thr255Ser (c.763A>T)?

AlphaMissense predicts ambiguous (score 0.4044) — an in-silico prediction, not a clinical call.

YAP1 p.Thr255Ser

c.763A>T · VCV3471611

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4044 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4044	ambiguous
REVEL	0.528	indeterminate
SaProt	LLR -8.51	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 119 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	23.7	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 0.00017% European (non-Finnish) · 2/1,179,558 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,020 alleles · very rare exomes 1/1,461,114 · genomes 1/151,906 · joint denominator

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.Thr255Ser
Coding: c.763A>T
MANE Select: NM_001130145
Type: single nucleotide variant
Location: chr11:102186092 (GRCh38)
Gene constraint: LOEUF 0.212 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 58.46 · 41 PDB
Residue 255: the ww 2 domain; a β-strand

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-thr255ser (accessed [today's date]).

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