Is YAP1 p.Pro33= (c.99C>G) pathogenic?

YAP1 p.Pro33= (c.99C>G) is classified Likely benign in YAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-22). Ultra-rare (popmax 0.0263%, afr).

How common is YAP1 p.Pro33= (c.99C>G) in the general population?

YAP1 p.Pro33= (c.99C>G) is ultra-rare (popmax 0.0263%, afr) (gnomAD).

YAP1 p.Pro33=

c.99C>G · VCV4913630

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0263%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.2	GERP -1.9
Overall
CADD	7.22	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0263% African / African-American · 18/68,370 alleles

Filtering AF 0.017% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.014%

Overall 0.00127% 19/1,500,596 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0263%	3,798
Admixed American	0.00224%	44,692

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.Pro33=
Coding: c.99C>G
MANE Select: NM_001130145
Type: single nucleotide variant
Location: chr11:102110947 (GRCh38)
Gene constraint: LOEUF 0.212 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 58.46 · 41 PDB
Residue 33: the 'disordered' 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-pro33 (accessed [today's date]).

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