Is ACTA1 p.Ser237del (c.700TCC[3]) pathogenic?

ACTA1 p.Ser237del (c.700TCC[3]) is classified Uncertain significance in ACTA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-06). Very rare (popmax 0.00134%, afr); Associated with congenital myopathy 2a, typical, autosomal dominant.

What condition is associated with ACTA1 p.Ser237del (c.700TCC[3])?

ACTA1 p.Ser237del (c.700TCC[3]) is associated with congenital myopathy 2a, typical, autosomal dominant (ClinVar).

How common is ACTA1 p.Ser237del (c.700TCC[3]) in the general population?

ACTA1 p.Ser237del (c.700TCC[3]) is very rare (popmax 0.00134%, afr) (gnomAD).

ACTA1 p.Ser237del

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.700TCC[3] · VCV4775820

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

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 6.3	GERP 1.7, phastCons 1
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,884 alleles

Overall 0.000124% 2/1,612,956 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,884
European (non-Finnish)	8.48e-05%	1,179,888

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ACTA1
Protein: p.Ser237del
Coding: c.700TCC[3]
MANE Select: NM_001100
Type: Microsatellite
Location: chr1:229432091 (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.Ser237Pro Uncertain significance ★ ⚠ same residue
ACTA1 c.455-18_455-15del Uncertain significance ★ same condition
ACTA1 c.455-20TC[2] Uncertain significance ★ same condition
ACTA1 c.990+6TGG[3] Likely benign ★ 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
ACTA1 p.Asp181fs 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-ser237del (accessed [today's date]).

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