Is ACTA1 p.Val47Glu (c.140_141delinsAA) pathogenic?

ACTA1 p.Val47Glu (c.140141delinsAA) is classified Likely pathogenic in ACTA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-27). Associated with congenital myopathy 2a, typical, autosomal dominant.

What condition is associated with ACTA1 p.Val47Glu (c.140_141delinsAA)?

ACTA1 p.Val47Glu (c.140_141delinsAA) is associated with congenital myopathy 2a, typical, autosomal dominant (ClinVar).

ACTA1 p.Val47Glu

Q: How is Congenital myopathy with excess of thin filaments inherited?

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

c.140_141delinsAA · VCV3572944

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

Conditions

congenital myopathy 2a, typical, autosomal dominant

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 -2	GERP -5.2
Regional constraint	o/e 0.33	constrained · MANE · 1,613 bp · p 1.6e-54 · regional, not allelic

Variant & gene context

Gene: ACTA1
Protein: p.Val47Glu
Coding: c.140_141delinsAA
MANE Select: NM_001100
Type: Indel
Location: chr1:229432869 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.21 · 5 PDB
Residue 47: a β-strand

Full ACTA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital myopathy 2a, typical, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital myopathy with excess of thin filaments (Orphanet):

Inheritance: Autosomal dominant

Similar variants

ACTA1 p.Val47= Likely benign ★★ same residue
ACTA1 c.130-11_130-10delinsTC Uncertain significance ★ same condition
ACTA1 p.Ala233Asn Uncertain significance ★ same condition
ACTA1 p.Ala274Ser Uncertain significance ★ same condition
ACTA1 p.Ala28Cys Uncertain significance ★ same condition
ACTA1 c.617-5C>A Likely pathogenic ★★★ same condition
ACTA1 c.990+1G>T Pathogenic ★★★ same condition
ACTA1 p.Asp13Asn 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/acta1-p-val47glu (accessed [today's date]).

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