Is ACTA1 p.Pro104= (c.312C>G) pathogenic?

ACTA1 p.Pro104= (c.312C>G) is classified Likely benign in ACTA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-07-05). Very rare (popmax 6.84e-05%); Associated with congenital myopathy 2a, typical, autosomal dominant.

What condition is associated with ACTA1 p.Pro104= (c.312C>G)?

ACTA1 p.Pro104= (c.312C>G) is associated with congenital myopathy 2a, typical, autosomal dominant (ClinVar).

How common is ACTA1 p.Pro104= (c.312C>G) in the general population?

ACTA1 p.Pro104= (c.312C>G) is very rare (popmax 6.84e-05%) (gnomAD).

ACTA1 p.Pro104=

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.312C>G · rs1289671104 · VCV1147290

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

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 -0.58	GERP -2.2, phastCons 0.002
Overall
CADD	8.766	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,888 alleles · very rare

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.Pro104=
Coding: c.312C>G
MANE Select: NM_001100
dbSNP: rs1289671104
Type: single nucleotide variant
Location: chr1:229432698 (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.Pro104His 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-pro104 (accessed [today's date]).

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