Is ACTA2 p.Leu301= (c.903A>G) pathogenic?

ACTA2 p.Leu301= (c.903A>G) is classified Likely benign in ACTA2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-24). Ultra-rare (popmax 0.0107%, afr); Associated with familial thoracic aortic aneurysm and aortic dissection.

How common is ACTA2 p.Leu301= (c.903A>G) in the general population?

ACTA2 p.Leu301= (c.903A>G) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

ACTA2 p.Leu301=

Q: What condition is associated with ACTA2 p.Leu301= (c.903A>G)?

ACTA2 p.Leu301= (c.903A>G) is associated with familial thoracic aortic aneurysm and aortic dissection, aortic aneurysm, familial thoracic 6 (ClinVar).

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.903A>G · rs372824072 · VCV412814

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Conditions

familial thoracic aortic aneurysm and aortic dissection

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

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 0.58	GERP -1, phastCons 1
Overall
CADD	7.884	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0107% African / African-American · 8/75,038 alleles

Filtering AF 0.00527% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00112% 18/1,614,060 alleles · ultra-rare exomes 10/1,461,782 · genomes 8/152,278 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,380
Remaining individualsnot grpmax-eligible	0.0096%	10,417
Admixed American	0.00666%	15,004

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.Leu301=
Coding: c.903A>G
MANE Select: NM_001613
dbSNP: rs372824072
Type: single nucleotide variant
Location: chr10:88938148 (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

Also linked: aortic aneurysm, familial thoracic 6

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-leu301 (accessed [today's date]).

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