Is TEAD1 p.Pro26Ser (c.76C>T) pathogenic?

TEAD1 p.Pro26Ser (c.76C>T) is classified Uncertain significance in TEAD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-18). AlphaMissense: likely benign (0.078); Absent from gnomAD v4.1.

How common is TEAD1 p.Pro26Ser (c.76C>T) in the general population?

TEAD1 p.Pro26Ser (c.76C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TEAD1 p.Pro26Ser (c.76C>T)?

AlphaMissense predicts likely benign (score 0.078) — an in-silico prediction, not a clinical call.

TEAD1 p.Pro26Ser

c.76C>T · rs369254497 · VCV836948

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.078 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.078	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -6.78	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 1, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 114 bp · p 0.52 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TEAD1
Protein: p.Pro26Ser
Coding: c.76C>T
MANE Select: NM_021961
dbSNP: rs369254497
Type: single nucleotide variant
Location: chr11:12764308 (GRCh38)
Gene constraint: LOEUF 0.276 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.43 · 14 PDB
Residue 26: the 'disordered' region

Full TEAD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TEAD1 p.Pro26Gln Uncertain significance ★★ ⚠ same residue
TEAD1 c.575-3C>T Uncertain significance ★★ same type
TEAD1 p.Ala123Val Uncertain significance ★★ same type
TEAD1 p.Ala188Thr Uncertain significance ★★ ⚠ same type
TEAD1 p.Ala200Val Uncertain significance ★★ ⚠ same type
TEAD1 p.Ala205Pro Uncertain significance ★★ ⚠ same type
TEAD1 p.Ala23Val Uncertain significance ★★ ⚠ same type
TEAD1 p.Arg147His Uncertain significance ★★ ⚠ 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/tead1-p-pro26ser (accessed [today's date]).

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