Is ACTA2 p.Pro335= (c.1005G>A) pathogenic?

ACTA2 p.Pro335= (c.1005G>A) is classified Uncertain significance in ACTA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-16). Very rare (popmax 0.00333%, amr); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with ACTA2 p.Pro335= (c.1005G>A)?

ACTA2 p.Pro335= (c.1005G>A) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is ACTA2 p.Pro335= (c.1005G>A) in the general population?

ACTA2 p.Pro335= (c.1005G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

ACTA2 p.Pro335=

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.1005G>A · rs775742052 · VCV1313236

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

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 -11	GERP -4
Overall
CADD	11.59	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,006 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000342% 5/1,461,532 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,003
East Asian	0.00223%	44,862
European (non-Finnish)	0.00017%	589,883

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.Pro335=
Coding: c.1005G>A
dbSNP: rs775742052
Type: single nucleotide variant
Location: chr10:88935352 (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-pro335 (accessed [today's date]).

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