Is TEAD3 p.Pro146Ser (c.436C>T) pathogenic?

TEAD3 p.Pro146Ser (c.436C>T) is classified Uncertain significance in TEAD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-26). AlphaMissense: likely benign (0.0736); Very rare (popmax 0.00882%, nfe).

How common is TEAD3 p.Pro146Ser (c.436C>T) in the general population?

TEAD3 p.Pro146Ser (c.436C>T) is very rare (popmax 0.00882%, nfe) (gnomAD).

What do computational predictors say about TEAD3 p.Pro146Ser (c.436C>T)?

AlphaMissense predicts likely benign (score 0.0736) — an in-silico prediction, not a clinical call.

TEAD3 p.Pro146Ser

c.436C>T · VCV3454554

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0736 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00882%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0736	likely benign
REVEL	0.164	moderately benign-leaning
SaProt	LLR -5.75	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 12	GERP 1.8, phastCons 1
Overall
CADD	23.1	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

Grpmax group 0.00882% European (non-Finnish) · 104/1,179,422 alleles

Filtering AF 0.00741% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00693%

Overall 0.00657% 106/1,612,672 alleles · very rare exomes 102/1,460,448 · genomes 4/152,224 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00882%	11,341
Remaining individualsnot grpmax-eligible	0.0032%	31,213

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: TEAD3
Protein: p.Pro146Ser
Coding: c.436C>T
MANE Select: NM_003214
Type: single nucleotide variant
Location: chr6:35478478 (GRCh38)
Gene constraint: LOEUF 0.435 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.53 · 10 PDB

Full TEAD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TULP1 p.Phe491Leu Pathogenic/Likely pathogenic ★★ same type
TEAD3 p.Ala127Thr Uncertain significance ★ ⚠ same type
TEAD3 p.Ala257Thr Uncertain significance ★ ⚠ same type
TEAD3 p.Ala265Thr Uncertain significance ★ ⚠ same type
TEAD3 p.Ala8Pro Uncertain significance ★ ⚠ same type
TEAD3 p.Arg218Cys Uncertain significance ★ ⚠ same type
TEAD3 p.Arg224Gln Uncertain significance ★ ⚠ same type
TEAD3 p.Arg226Gln 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/tead3-p-pro146ser (accessed [today's date]).

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