Is ACTA2 p.Ala367Val (c.1100C>T) pathogenic?

ACTA2 p.Ala367Val (c.1100C>T) is classified Uncertain significance in ACTA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-14). AlphaMissense: ambiguous (0.5408); Absent from gnomAD v4.1; Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with ACTA2 p.Ala367Val (c.1100C>T)?

ACTA2 p.Ala367Val (c.1100C>T) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is ACTA2 p.Ala367Val (c.1100C>T) in the general population?

ACTA2 p.Ala367Val (c.1100C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTA2 p.Ala367Val (c.1100C>T)?

AlphaMissense predicts ambiguous (score 0.5408) — an in-silico prediction, not a clinical call.

ACTA2 p.Ala367Val

Q: How is Familial thoracic aortic aneurysm and aortic dissection inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.1100C>T · rs1589388776 · VCV923191

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5408 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

familial thoracic aortic aneurysm and aortic dissection

Computational evidence

Protein change
AlphaMissense	0.5408	ambiguous
REVEL	0.559	indeterminate
SaProt	LLR -9.25	tolerated
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.47	unconstrained · MANE · 14 kb · p 5.8e-32 · regional, not allelic
Overall
CADD	28.2	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

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: ACTA2
Protein: p.Ala367Val
Coding: c.1100C>T
dbSNP: rs1589388776
Type: single nucleotide variant
Location: chr10:88935257 (GRCh38)

Full ACTA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial thoracic aortic aneurysm and aortic dissection — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial thoracic aortic aneurysm and aortic dissection (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

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/acta2-p-ala367val (accessed [today's date]).

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