Is ACTA1 p.Gln248= (c.744G>A) pathogenic?

ACTA1 p.Gln248= (c.744G>A) is classified Likely benign in ACTA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-06). Very rare (popmax 0.00401%, afr); Associated with congenital myopathy 2a, typical, autosomal dominant.

What condition is associated with ACTA1 p.Gln248= (c.744G>A)?

ACTA1 p.Gln248= (c.744G>A) is associated with congenital myopathy 2a, typical, autosomal dominant (ClinVar).

How common is ACTA1 p.Gln248= (c.744G>A) in the general population?

ACTA1 p.Gln248= (c.744G>A) is very rare (popmax 0.00401%, afr) (gnomAD).

ACTA1 p.Gln248=

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.744G>A · rs1331857493 · VCV1589183

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00401%, 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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -0.32, phastCons 1
Overall
CADD	12.05	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,830 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00031% 5/1,612,380 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,943
South Asian	0.0011%	91,004
European (non-Finnish)	8.48e-05%	1,179,802

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.Gln248=
Coding: c.744G>A
MANE Select: NM_001100
dbSNP: rs1331857493
Type: single nucleotide variant
Location: chr1:229432058 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.21 · 5 PDB
Residue 248: a UniProt-annotated variant site (in cmyo2a)

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.Gln248Lys 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
ACTA1 p.Glu102Lys 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-gln248 (accessed [today's date]).

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