Is ACTA2 p.Thr196= (c.588T>G) pathogenic?

ACTA2 p.Thr196= (c.588T>G) is classified Likely benign in ACTA2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-08-06). Absent from gnomAD v4.1; Associated with familial thoracic aortic aneurysm and aortic dissection.

How common is ACTA2 p.Thr196= (c.588T>G) in the general population?

ACTA2 p.Thr196= (c.588T>G) is absent from gnomAD v4.1 (gnomAD).

ACTA2 p.Thr196=

Q: What condition is associated with ACTA2 p.Thr196= (c.588T>G)?

ACTA2 p.Thr196= (c.588T>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.588T>G · rs2494537581 · VCV2911132

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Pangolin	Δ0.27	gain · loss 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP -11	GERP -4
Overall
CADD	0.198	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACTA2
Protein: p.Thr196=
Coding: c.588T>G
MANE Select: NM_001613
dbSNP: rs2494537581
Type: single nucleotide variant
Location: chr10:88941257 (GRCh38)
Gene constraint: LOEUF 0.472 · pLI 0.99 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 95.43
Residue 196: a UniProt-annotated variant site (in)

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

Similar variants

ACTA2 p.Thr196fs Uncertain significance ★ same residue
ACTA2 p.Thr196Ser Uncertain significance ★ ⚠ same residue
ACTA2 p.Arg118Gln Pathogenic/Likely pathogenic ★★ same condition
ACTA2 p.Arg149Cys Pathogenic ★★ same condition
ACTA2 p.Arg149Leu Pathogenic/Likely pathogenic ★★ same condition
ACTA2 p.Arg179Cys Pathogenic ★★ same condition
ACTA2 p.Arg179His 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-thr196 (accessed [today's date]).

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