Is ACTC1 p.Asp294Glu (c.882C>A) pathogenic?

ACTC1 p.Asp294Glu (c.882C>A) is classified Uncertain significance in ACTC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-25). AlphaMissense: likely pathogenic (0.8513); Absent from gnomAD v4.1; Associated with dilated cardiomyopathy 1R.

What condition is associated with ACTC1 p.Asp294Glu (c.882C>A)?

ACTC1 p.Asp294Glu (c.882C>A) is associated with dilated cardiomyopathy 1R, hypertrophic cardiomyopathy 11, atrial septal defect 5 (ClinVar).

How common is ACTC1 p.Asp294Glu (c.882C>A) in the general population?

ACTC1 p.Asp294Glu (c.882C>A) is absent from gnomAD v4.1 (gnomAD).

How is Left ventricular noncompaction inherited?

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

What do computational predictors say about ACTC1 p.Asp294Glu (c.882C>A)?

AlphaMissense predicts likely pathogenic (score 0.8513) — an in-silico prediction, not a clinical call.

ACTC1 p.Asp294Glu

c.882C>A · VCV4783294

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8513 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

dilated cardiomyopathy 1R

Computational evidence

Protein change
AlphaMissense	0.8513	likely pathogenic
REVEL	0.522	indeterminate
SaProt	LLR -9.49	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.1	GERP -0.65, phastCons 1
Regional constraint	o/e 0.35	constrained · MANE · 850 bp · p 1.5e-13 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACTC1
Protein: p.Asp294Glu
Coding: c.882C>A
Type: single nucleotide variant
Location: chr15:34791222 (GRCh38)

Full ACTC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dilated cardiomyopathy 1R — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypertrophic cardiomyopathy 11 atrial septal defect 5

For Left ventricular noncompaction (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages

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/actc1-p-asp294glu (accessed [today's date]).

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