Is ACTA1 p.Phe92del (c.275_277del) pathogenic?

ACTA1 p.Phe92del (c.275277del) is classified Pathogenic/Likely pathogenic in ACTA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-16). Absent from gnomAD; Associated with congenital myopathy 2a, typical, autosomal dominant.

What condition is associated with ACTA1 p.Phe92del (c.275_277del)?

ACTA1 p.Phe92del (c.275_277del) is associated with congenital myopathy 2a, typical, autosomal dominant (ClinVar).

How common is ACTA1 p.Phe92del (c.275_277del) in the general population?

ACTA1 p.Phe92del (c.275_277del) is absent from gnomAD (gnomAD).

ACTA1 p.Phe92del

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.275_277del · rs1558082053 · VCV570214

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

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 7.8	GERP 2.6, 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: ACTA1
Protein: p.Phe92del
Coding: c.275_277del
MANE Select: NM_001100
dbSNP: rs1558082053
Type: Deletion
Location: chr1:229432733 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.21 · 5 PDB
Residue 92: 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.Asp181fs Pathogenic ★★★ same condition
ACTA1 p.Ala146fs Pathogenic/Likely pathogenic ★★ same condition
ACTA1 p.Asn117fs Likely pathogenic ★ same condition
ACTA1 p.Glu336fs Pathogenic ★ same condition
ACTA1 p.Leu238fs Pathogenic ★ same condition
ACTA1 p.Lys328del Pathogenic ★ same condition
ACTA1 p.Lys52fs Pathogenic ★ same condition
ACTA1 p.Met134fs 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-phe92del (accessed [today's date]).

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