Is TEAD1 p.Pro166Ala (c.496C>G) pathogenic?

TEAD1 p.Pro166Ala (c.496C>G) is classified Conflicting classifications of pathogenicity in TEAD1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-26). AlphaMissense: likely benign (0.0584); Very rare (popmax 0.00667%, amr); Associated with Inborn genetic diseases.

What condition is associated with TEAD1 p.Pro166Ala (c.496C>G)?

TEAD1 p.Pro166Ala (c.496C>G) is associated with Inborn genetic diseases (ClinVar).

How common is TEAD1 p.Pro166Ala (c.496C>G) in the general population?

TEAD1 p.Pro166Ala (c.496C>G) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about TEAD1 p.Pro166Ala (c.496C>G)?

AlphaMissense predicts likely benign (score 0.0584) — an in-silico prediction, not a clinical call.

TEAD1 p.Pro166Ala

c.496C>G · rs746873807 · VCV1985846

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0584 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0584	likely benign
REVEL	0.182	moderately benign-leaning
SaProt	LLR -7.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.25	donor loss · deltas
Pangolin	Δ0.35	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 22 kb · p 0.96 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/60,010 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00403% 65/1,614,048 alleles · very rare exomes 64/1,461,872 · genomes 1/152,176 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.142%	705
Remaining individualsnot grpmax-eligible	0.0096%	10,413
Admixed Americangrpmax	0.00667%	15,002
European (non-Finnish)	0.0011%	90,773

Ashkenazi Jewish 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: TEAD1
Protein: p.Pro166Ala
Coding: c.496C>G
MANE Select: NM_021961
dbSNP: rs746873807
Type: single nucleotide variant
Location: chr11:12881035 (GRCh38)
Gene constraint: LOEUF 0.276 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.43 · 14 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TEAD1 p.Ala123Val Uncertain significance ★★ same condition
TEAD1 p.Ala188Thr Uncertain significance ★★ ⚠ same condition
TEAD1 p.Ala205Pro Uncertain significance ★★ ⚠ same condition
TEAD1 p.Asn235Ser Uncertain significance ★★ ⚠ same condition
TEAD1 p.Asn297Asp Uncertain significance ★★ ⚠ same condition
TEAD1 p.Cys405Ser Uncertain significance ★★ ⚠ same condition
TEAD1 p.Glu313Lys Uncertain significance ★★ ⚠ same condition
TEAD1 p.Gly303Glu Uncertain significance ★★ same condition

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-pro166ala (accessed [today's date]).

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