Is ACTA2 c.*4A>G pathogenic?

ACTA2 c.4A>G is classified Uncertain significance in ACTA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). Very rare (popmax 0.00134%, afr); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with ACTA2 c.*4A>G?

ACTA2 c.*4A>G is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is ACTA2 c.*4A>G in the general population?

ACTA2 c.*4A>G is very rare (popmax 0.00134%, afr) (gnomAD).

ACTA2 c.*4A>G

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.

VCV4758619

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

familial thoracic aortic aneurysm and aortic dissection

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 -0.8	GERP -2.2, phastCons 0.001
Non-coding constraint	Z 2.83	1 kb window · o/e 0.81 · regional · uncalibrated
Overall
CADD	9.399	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,846 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000806% 13/1,612,618 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,846
European (non-Finnish)	0.00102%	98,308

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
Coding: c.*4A>G
Type: single nucleotide variant
Location: chr10:88935219 (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-c-star-4a-g (accessed [today's date]).

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