Is ACTA2 p.Thr8= (c.24T>G) pathogenic?

ACTA2 p.Thr8= (c.24T>G) is classified Uncertain significance in ACTA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-04-27). Absent from gnomAD v4.1; Associated with multisystemic smooth muscle dysfunction syndrome.

What condition is associated with ACTA2 p.Thr8= (c.24T>G)?

ACTA2 p.Thr8= (c.24T>G) is associated with multisystemic smooth muscle dysfunction syndrome, aortic aneurysm, familial thoracic 6 (ClinVar).

How common is ACTA2 p.Thr8= (c.24T>G) in the general population?

ACTA2 p.Thr8= (c.24T>G) is absent from gnomAD v4.1 (gnomAD).

ACTA2 p.Thr8=

Q: How is Multisystemic smooth muscle dysfunction syndrome inherited?

Typically Unknown (Orphanet). A genetic counselor can assess individual risk for a family.

c.24T>G · rs1589400483 · VCV879816

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

multisystemic smooth muscle dysfunction syndrome

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
Constraint at this position
Conservation	phyloP -4.9	GERP -3.7
Overall
CADD	1.815	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.Thr8=
Coding: c.24T>G
MANE Select: NM_001613
dbSNP: rs1589400483
Type: single nucleotide variant
Location: chr10:88948907 (GRCh38)
Gene constraint: LOEUF 0.472 · pLI 0.99 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 95.43

Full ACTA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

multisystemic smooth muscle dysfunction syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: aortic aneurysm, familial thoracic 6

For Multisystemic smooth muscle dysfunction syndrome (Orphanet):

Inheritance: Unknown
Onset: Infancy

Similar variants

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
ACTA2 p.Arg198His Pathogenic/Likely pathogenic ★★ same condition
ACTA2 p.Arg256Cys 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-thr8 (accessed [today's date]).

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