Is YAP1 p.Pro278Ser (c.832C>T) pathogenic?

YAP1 p.Pro278Ser (c.832C>T) is classified Likely benign in YAP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-04-02). AlphaMissense: likely benign (0.1713); Rare (popmax 0.119%, amr); Associated with uveal coloboma-cleft lip and palate-intellectual disability.

What condition is associated with YAP1 p.Pro278Ser (c.832C>T)?

YAP1 p.Pro278Ser (c.832C>T) is associated with uveal coloboma-cleft lip and palate-intellectual disability (ClinVar).

How common is YAP1 p.Pro278Ser (c.832C>T) in the general population?

YAP1 p.Pro278Ser (c.832C>T) is rare (popmax 0.119%, amr) (gnomAD).

What do computational predictors say about YAP1 p.Pro278Ser (c.832C>T)?

AlphaMissense predicts likely benign (score 0.1713) — an in-silico prediction, not a clinical call.

YAP1 p.Pro278Ser

c.832C>T · rs61746398 · VCV802714

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1713 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.119%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

uveal coloboma-cleft lip and palate-intellectual disability

Computational evidence

Protein change
AlphaMissense	0.1713	likely benign
REVEL	0.17	moderately benign-leaning
SaProt	LLR -8.44	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 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	24.7	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 0.119% Admixed American · 70/58,880 alleles

Filtering AF 0.0995% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0975%

Overall 0.0838% 1,341/1,601,064 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.119%	841
European (non-Finnish)	0.104%	958
Remaining individualsnot grpmax-eligible	0.0486%	2,059
African / African-American	0.0188%	5,319
Finnishnot grpmax-eligible	0.00314%	31,887

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.Pro278Ser
Coding: c.832C>T
MANE Select: NM_001130145
dbSNP: rs61746398
Type: single nucleotide variant
Location: chr11:102205922 (GRCh38)
Gene constraint: LOEUF 0.212 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 58.46 · 41 PDB
Residue 278: the 'disordered' region

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

Disease context

uveal coloboma-cleft lip and palate-intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

YAP1 c.1276+42G>C Benign ★★ same condition
YAP1 p.Met86Thr Pathogenic ★ ⚠ same condition
YAP1 p.Ser229Ter Likely pathogenic ★ same condition
YAP1 c.985-1G>C Uncertain significance ★ same condition
YAP1 p.Arg327Trp Uncertain significance ★ ⚠ same condition
YAP1 p.Lys254Arg Uncertain significance ★ ⚠ same condition
YAP1 p.Ser257Phe Uncertain significance ★ ⚠ same condition
YAP1 p.Glu356Ter Pathogenic same condition

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-pro278ser (accessed [today's date]).

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