Is ACTA2 p.Ala349= (c.1047C>T) pathogenic?

ACTA2 p.Ala349= (c.1047C>T) is classified Likely benign in ACTA2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-04-23). Ultra-rare (popmax 0.0267%, afr); Associated with aortic aneurysm, familial thoracic 6.

What condition is associated with ACTA2 p.Ala349= (c.1047C>T)?

ACTA2 p.Ala349= (c.1047C>T) is associated with aortic aneurysm, familial thoracic 6, familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is ACTA2 p.Ala349= (c.1047C>T) in the general population?

ACTA2 p.Ala349= (c.1047C>T) is ultra-rare (popmax 0.0267%, afr) (gnomAD).

ACTA2 p.Ala349=

Q: How is Multisystemic smooth muscle dysfunction syndrome inherited?

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

c.1047C>T · rs111352790 · VCV469082

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, afr)

Conditions

aortic aneurysm, familial thoracic 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.2	GERP -0.81, phastCons 0.88
Overall
CADD	15.45	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% African / African-American · 20/75,030 alleles

Filtering AF 0.0177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00192% 31/1,613,984 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0267%	3,752
Remaining individualsnot grpmax-eligible	0.0176%	5,682

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: ACTA2
Protein: p.Ala349=
Coding: c.1047C>T
dbSNP: rs111352790
Type: single nucleotide variant
Location: chr10:88935310 (GRCh38)

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

Disease context

aortic aneurysm, familial thoracic 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial thoracic aortic aneurysm and aortic dissection

For Multisystemic smooth muscle dysfunction syndrome (Orphanet):

Inheritance: Unknown
Onset: Infancy

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-ala349 (accessed [today's date]).

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