Is ACTA1 p.Asp83= (c.249C>T) pathogenic?

ACTA1 p.Asp83= (c.249C>T) is classified Likely benign in ACTA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-19). Absent from gnomAD v4.1; Associated with congenital myopathy 2a, typical, autosomal dominant.

What condition is associated with ACTA1 p.Asp83= (c.249C>T)?

ACTA1 p.Asp83= (c.249C>T) is associated with congenital myopathy 2a, typical, autosomal dominant (ClinVar).

How common is ACTA1 p.Asp83= (c.249C>T) in the general population?

ACTA1 p.Asp83= (c.249C>T) is absent from gnomAD v4.1 (gnomAD).

ACTA1 p.Asp83=

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.249C>T · rs1571893843 · VCV2114348

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP -0.18, phastCons 1
Overall
CADD	11.19	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: ACTA1
Protein: p.Asp83=
Coding: c.249C>T
MANE Select: NM_001100
dbSNP: rs1571893843
Type: single nucleotide variant
Location: chr1:229432761 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.21 · 5 PDB
Residue 83: an α-helix

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.Asp83His Uncertain significance ★ same residue
ACTA1 p.Asp83Asn Uncertain significance ⚠ same residue
ACTA1 c.617-5C>A Likely pathogenic ★★★ same condition
ACTA1 c.990+1G>T Pathogenic ★★★ same condition
ACTA1 p.Asp13Asn Likely pathogenic ★★★ same condition
ACTA1 p.Asp290His Pathogenic ★★★ same condition
ACTA1 p.Asp58Asn Likely pathogenic ★★★ same condition
ACTA1 p.Cys376Phe 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-asp83 (accessed [today's date]).

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