Is ACTA1 p.Ile36= (c.108C>T) pathogenic?

ACTA1 p.Ile36= (c.108C>T) is classified Conflicting classifications of pathogenicity in ACTA1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-05-26). Rare (popmax 0.181%, mid); Associated with congenital fiber-type disproportion myopathy.

What condition is associated with ACTA1 p.Ile36= (c.108C>T)?

ACTA1 p.Ile36= (c.108C>T) is associated with congenital fiber-type disproportion myopathy, congenital myopathy 2a, typical, autosomal dominant, familial restrictive cardiomyopathy (ClinVar).

How common is ACTA1 p.Ile36= (c.108C>T) in the general population?

ACTA1 p.Ile36= (c.108C>T) is rare (popmax 0.181%, mid) (gnomAD).

How is Congenital fiber-type disproportion myopathy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ACTA1 p.Ile36=

c.108C>T · rs143948837 · VCV296059

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.181%, mid)

Conditions

congenital fiber-type disproportion myopathy

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 2	GERP -1.8, phastCons 1
Overall
CADD	11.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.181% Middle Eastern · 11/6,082 alleles

Filtering AF 0.101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0784%

Overall 0.00217% 35/1,613,612 alleles · rare exomes 33/1,461,396 · genomes 2/152,216 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.181%	553
European (non-Finnish)	0.00195%	51,297
Remaining individualsnot grpmax-eligible	0.0016%	62,460

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.Ile36=
Coding: c.108C>T
MANE Select: NM_001100
dbSNP: rs143948837
Type: single nucleotide variant
Location: chr1:229433008 (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 fiber-type disproportion myopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital myopathy 2a, typical, autosomal dominant familial restrictive cardiomyopathy

For Congenital fiber-type disproportion myopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal

Similar variants

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
ACTA1 p.Glu336Ala 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-ile36 (accessed [today's date]).

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