Is ACTA1 p.Asp313fs (c.936del) pathogenic?

ACTA1 p.Asp313fs (c.936del) is classified Likely pathogenic in ACTA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-10). Very rare (popmax 0.00133%, afr); Associated with alpha-actinopathy.

What condition is associated with ACTA1 p.Asp313fs (c.936del)?

ACTA1 p.Asp313fs (c.936del) is associated with alpha-actinopathy (ClinVar).

How common is ACTA1 p.Asp313fs (c.936del) in the general population?

ACTA1 p.Asp313fs (c.936del) is very rare (popmax 0.00133%, afr) (gnomAD).

ACTA1 p.Asp313fs

c.936del · rs2527436130 · VCV2627920

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

alpha-actinopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,058 alleles

Overall 6.84e-05% 1/1,461,870 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.Asp313fs
Coding: c.936del
MANE Select: NM_001100
dbSNP: rs2527436130
Type: Deletion
Location: chr1:229431775 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.21 · 5 PDB
Residue 313: an α-helix

Full ACTA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

alpha-actinopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACTA1 p.Asp181fs Pathogenic ★★★ same condition
ACTA1 p.Glu363_Tyr364insTer Likely pathogenic ★★★ same condition
ACTA1 c.809-35del Benign ★★★ same condition
ACTA1 p.Asp313His 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

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-asp313fs (accessed [today's date]).

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