Is YAP1 p.Pro368= (c.1104C>T) pathogenic?

YAP1 p.Pro368= (c.1104C>T) is classified Benign in YAP1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-15). Rare (popmax 0.995%, nfe).

How common is YAP1 p.Pro368= (c.1104C>T) in the general population?

YAP1 p.Pro368= (c.1104C>T) is rare (popmax 0.995%, nfe) (gnomAD).

YAP1 p.Pro368=

c.1104C>T · rs61749258 · VCV789314

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.995%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.074	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.6	GERP -3.9
Overall
CADD	9.281	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.995% European (non-Finnish) · 11,744/1,179,984 alleles

Filtering AF 0.98% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.974%

Overall 0.816% 13,175/1,614,076 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.97%	51
European (non-Finnish)grpmax	0.995%	100
Remaining individualsnot grpmax-eligible	0.771%	130
South Asian	0.4%	250
Admixed American	0.363%	275
Ashkenazi Jewishnot grpmax-eligible	0.284%	352
Finnishnot grpmax-eligible	0.242%	413
Middle Eastern	0.198%	505
African / African-American	0.131%	766

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro368=
Coding: c.1104C>T
MANE Select: NM_001130145
dbSNP: rs61749258
Type: single nucleotide variant
Location: chr11:102223693 (GRCh38)
Gene constraint: LOEUF 0.212 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 58.46 · 41 PDB
Residue 368: the 'transactivation domain' region; 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-pro368 (accessed [today's date]).

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