Is ACTA2 p.Arg179= (c.537T>G) pathogenic?

ACTA2 p.Arg179= (c.537T>G) is classified Likely benign in ACTA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-30). Very rare (popmax 0.00269%, afr); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with ACTA2 p.Arg179= (c.537T>G)?

ACTA2 p.Arg179= (c.537T>G) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is ACTA2 p.Arg179= (c.537T>G) in the general population?

ACTA2 p.Arg179= (c.537T>G) is very rare (popmax 0.00269%, afr) (gnomAD).

ACTA2 p.Arg179=

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.537T>G · rs1301667023 · VCV3071352

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00269%, 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 assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.84	GERP -1.8, phastCons 0.97
Overall
CADD	9.117	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00269% African / African-American · 2/74,424 alleles

Filtering AF 0.000446% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000167%

Overall 0.00199% 3/150,986 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00269%	37,212
Remaining individualsnot grpmax-eligible	0.0016%	62,454

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.Arg179=
Coding: c.537T>G
MANE Select: NM_001613
dbSNP: rs1301667023
Type: single nucleotide variant
Location: chr10:88941308 (GRCh38)
Gene constraint: LOEUF 0.472 · pLI 0.99 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 95.43
Residue 179: a UniProt-annotated variant site (in smdys); a UniProt-annotated variant site (in mymy5 and smdys; disease phenotype include smooth muscle cells dysfunction in organs throughout the body with decreased contractile function in the iris, bladder and gastrointestinal tract)

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

Similar variants

ACTA2 p.Arg179Cys Pathogenic ★★ same residue
ACTA2 p.Arg179His Pathogenic ★★ same residue
ACTA2 p.Arg179delinsLeuAlaCys Uncertain significance ★ same residue
ACTA2 p.Arg179Leu Pathogenic same residue
ACTA2 p.Arg179Ser Pathogenic same residue
ACTA2 p.Arg118Gln Pathogenic/Likely pathogenic ★★ same condition
ACTA2 p.Arg149Cys Pathogenic ★★ same condition
ACTA2 p.Arg198Cys Pathogenic/Likely pathogenic ★★ same condition

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-arg179 (accessed [today's date]).

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