Is YAP1 p.Ser105Pro (c.313T>C) pathogenic?

YAP1 p.Ser105Pro (c.313T>C) is classified Uncertain significance in YAP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-09-22). AlphaMissense: likely pathogenic (0.9926); Ultra-rare (popmax 0.0329%, mid); Associated with YAP1-related disorder.

What condition is associated with YAP1 p.Ser105Pro (c.313T>C)?

YAP1 p.Ser105Pro (c.313T>C) is associated with YAP1-related disorder (ClinVar).

How common is YAP1 p.Ser105Pro (c.313T>C) in the general population?

YAP1 p.Ser105Pro (c.313T>C) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about YAP1 p.Ser105Pro (c.313T>C)?

AlphaMissense predicts likely pathogenic (score 0.9926) — an in-silico prediction, not a clinical call.

YAP1 p.Ser105Pro

c.313T>C · rs1391431049 · VCV2634825

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9926 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

YAP1-related disorder

Computational evidence

Protein change
AlphaMissense	0.9926	likely pathogenic
REVEL	0.124	moderately benign-leaning
SaProt	LLR -11.98	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP -1.3, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 119 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	23.3	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 0.0329% Middle Eastern · 2/6,082 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.00161% 26/1,612,178 alleles · ultra-rare exomes 23/1,460,318 · genomes 3/151,860 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,041
Remaining individualsnot grpmax-eligible	0.0048%	20,813
South Asian	0.0022%	45,537
Admixed American	0.00167%	59,970
European (non-Finnish)	0.00153%	65,532

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.Ser105Pro
Coding: c.313T>C
MANE Select: NM_001130145
dbSNP: rs1391431049
Type: single nucleotide variant
Location: chr11:102111161 (GRCh38)
Gene constraint: LOEUF 0.212 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 58.46 · 41 PDB
Residue 105: a modified residue (phosphoserine); the 'disordered' region

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

Disease context

YAP1-related disorder

Similar variants

YAP1 p.Arg394Ter Pathogenic ★ same condition
YAP1 c.321+8C>T Likely benign same condition
YAP1 p.Gly293= Likely benign same condition
YAP1 p.Tyr247fs Uncertain significance same condition
YAP1 p.Gln238Ter 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

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-ser105pro (accessed [today's date]).

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