Is ACTA2 p.Val47del (c.137TGG[1]) pathogenic?

ACTA2 p.Val47del (c.137TGG[1]) is classified Uncertain significance in ACTA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-20). Absent from gnomAD; Associated with aortic aneurysm, familial thoracic 6.

What condition is associated with ACTA2 p.Val47del (c.137TGG[1])?

ACTA2 p.Val47del (c.137TGG[1]) is associated with aortic aneurysm, familial thoracic 6 (ClinVar).

How common is ACTA2 p.Val47del (c.137TGG[1]) in the general population?

ACTA2 p.Val47del (c.137TGG[1]) is absent from gnomAD (gnomAD).

ACTA2 p.Val47del

Q: How is Multisystemic smooth muscle dysfunction syndrome inherited?

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

c.137TGG[1] · rs2494571122 · VCV2025269

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

aortic aneurysm, familial thoracic 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ACTA2
Protein: p.Val47del
Coding: c.137TGG[1]
MANE Select: NM_001613
dbSNP: rs2494571122
Type: Microsatellite
Location: chr10:88947374 (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

aortic aneurysm, familial thoracic 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Multisystemic smooth muscle dysfunction syndrome (Orphanet):

Inheritance: Unknown
Onset: Infancy

Similar variants

ACTA2 p.Val47Met Uncertain significance ★★ ⚠ same residue
ACTA2 p.Cys219fs Uncertain significance ★★ same condition
ACTA2 p.Ser340fs Uncertain significance ★★ same condition
ACTA2 p.Val47= Likely benign ★★ same residue
ACTA2 c.369+4_369+7del Uncertain significance ★ same condition
ACTA2 p.Arg118Gln Pathogenic/Likely pathogenic ★★ same condition
ACTA2 p.Arg149Cys Pathogenic ★★ same condition
ACTA2 p.Arg149Leu 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-val47del (accessed [today's date]).

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