Is ACTA1 p.Ala28Cys (c.82_83delinsTG) pathogenic?

ACTA1 p.Ala28Cys (c.8283delinsTG) is classified Uncertain significance in ACTA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-29). Absent from gnomAD; Associated with congenital myopathy 2a, typical, autosomal dominant.

What condition is associated with ACTA1 p.Ala28Cys (c.82_83delinsTG)?

ACTA1 p.Ala28Cys (c.82_83delinsTG) is associated with congenital myopathy 2a, typical, autosomal dominant (ClinVar).

How common is ACTA1 p.Ala28Cys (c.82_83delinsTG) in the general population?

ACTA1 p.Ala28Cys (c.82_83delinsTG) is absent from gnomAD (gnomAD).

ACTA1 p.Ala28Cys

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.82_83delinsTG · rs2102736585 · VCV1404743

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

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 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.33	constrained · MANE · 1,613 bp · p 1.6e-54 · regional, not allelic

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: ACTA1
Protein: p.Ala28Cys
Coding: c.82_83delinsTG
MANE Select: NM_001100
dbSNP: rs2102736585
Type: Indel
Location: chr1:229433033 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.21 · 5 PDB

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.Ala28Ser Uncertain significance ★★ ⚠ same residue
ACTA1 p.Ala28Pro Uncertain significance ★ ⚠ same residue
ACTA1 p.Ala28Thr Uncertain significance ★ ⚠ same residue
ACTA1 p.Val47Glu Likely pathogenic ★ same condition
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.Ala28Gly Uncertain significance ★ ⚠ same residue

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-ala28cys (accessed [today's date]).

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