Is YAP1 p.Pro48= (c.144C>T) pathogenic?

YAP1 p.Pro48= (c.144C>T) is classified Likely benign in YAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-15). Ultra-rare (popmax 0.0113%, amr).

How common is YAP1 p.Pro48= (c.144C>T) in the general population?

YAP1 p.Pro48= (c.144C>T) is ultra-rare (popmax 0.0113%, amr) (gnomAD).

YAP1 p.Pro48=

c.144C>T · rs745691073 · VCV727889

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0113%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.72	GERP -2.9, phastCons 0.025
Overall
CADD	12.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0113% Admixed American · 6/53,050 alleles

Filtering AF 0.00485% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00336%

Overall 0.000514% 8/1,557,710 alleles · ultra-rare exomes 6/1,405,604 · genomes 2/152,106 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0113%	8,842
Remaining individualsnot grpmax-eligible	0.00167%	60,050
European (non-Finnish)	8.66e-05%	1,154,848

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.Pro48=
Coding: c.144C>T
MANE Select: NM_001130145
dbSNP: rs745691073
Type: single nucleotide variant
Location: chr11:102110992 (GRCh38)
Gene constraint: LOEUF 0.212 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 58.46 · 41 PDB
Residue 48: 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-pro48 (accessed [today's date]).

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