Is TEAD2 p.Ser435Phe (c.1304C>T) pathogenic?

TEAD2 p.Ser435Phe (c.1304C>T) is classified Uncertain significance in TEAD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-07). AlphaMissense: likely pathogenic (0.9872); Absent from gnomAD v4.1.

How common is TEAD2 p.Ser435Phe (c.1304C>T) in the general population?

TEAD2 p.Ser435Phe (c.1304C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TEAD2 p.Ser435Phe (c.1304C>T)?

AlphaMissense predicts likely pathogenic (score 0.9872) — an in-silico prediction, not a clinical call.

TEAD2 p.Ser435Phe

c.1304C>T · VCV3805359

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9872 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9872	likely pathogenic
REVEL	0.637	indeterminate
SaProt	LLR -15.42	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.3	GERP 1.7, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 19 kb · p 0.0002 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S431F vs ClinVar S435F) — verify the residue.

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: TEAD2
Protein: p.Ser435Phe
Coding: c.1304C>T
MANE Select: NM_001256660
Type: single nucleotide variant
Location: chr19:49341376 (GRCh38)
Gene constraint: LOEUF 1.035 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.59 · 45 PDB
Residue 431 UniProt numbering: the 'transcriptional activation' region

Full TEAD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TEAD2 p.Gln116His Benign ★★ ⚠ same type
TEAD2 p.Gly226Ala Benign ★★ same type
TEAD2 p.Pro213Ser Benign ★★ same type
TEAD2 p.Ala224Thr Uncertain significance ★ ⚠ same type
TEAD2 p.Ala308Val Uncertain significance ★ ⚠ same type
TEAD2 p.Ala9Val Uncertain significance ★ ⚠ same type
TEAD2 p.Arg109Pro Uncertain significance ★ ⚠ same type
TEAD2 p.Arg225Gln 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/tead2-p-ser435phe (accessed [today's date]).

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