Is TEAD2 p.Ala9Val (c.26C>T) pathogenic?

TEAD2 p.Ala9Val (c.26C>T) is classified Uncertain significance in TEAD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). AlphaMissense: likely benign (0.0817); Ultra-rare (popmax 0.0634%, amr).

How common is TEAD2 p.Ala9Val (c.26C>T) in the general population?

TEAD2 p.Ala9Val (c.26C>T) is ultra-rare (popmax 0.0634%, amr) (gnomAD).

What do computational predictors say about TEAD2 p.Ala9Val (c.26C>T)?

AlphaMissense predicts likely benign (score 0.0817) — an in-silico prediction, not a clinical call.

TEAD2 p.Ala9Val

c.26C>T · rs746559026 · VCV2306031

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0817 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0634%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0817	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -7.71	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 6.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 19 kb · p 0.0002 · regional, not allelic
Overall
CADD	24.5	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 0.0634% Admixed American · 38/59,982 alleles

Filtering AF 0.0474% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0418%

Overall 0.00311% 50/1,607,088 alleles · ultra-rare exomes 38/1,454,860 · genomes 12/152,228 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0634%	1,578
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,789
Remaining individualsnot grpmax-eligible	0.00481%	20,805
European (non-Finnish)	0.000593%	168,545

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: TEAD2
Protein: p.Ala9Val
Coding: c.26C>T
MANE Select: NM_001256660
dbSNP: rs746559026
Type: single nucleotide variant
Location: chr19:49360050 (GRCh38)
Gene constraint: LOEUF 1.035 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.59 · 45 PDB
Residue 9: the 'disordered' 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.Arg109Pro Uncertain significance ★ ⚠ same type
TEAD2 p.Arg225Gln Uncertain significance ★ ⚠ same type
TEAD2 p.Arg225Trp 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-ala9val (accessed [today's date]).

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