Is ACTC1 p.Asp82Glu (c.246C>A) pathogenic?

ACTC1 p.Asp82Glu (c.246C>A) is classified Uncertain significance in ACTC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-30). AlphaMissense: likely pathogenic (0.8473); Absent from gnomAD v4.1; Associated with hypertrophic cardiomyopathy.

What condition is associated with ACTC1 p.Asp82Glu (c.246C>A)?

ACTC1 p.Asp82Glu (c.246C>A) is associated with hypertrophic cardiomyopathy, dilated cardiomyopathy 1R (ClinVar).

How common is ACTC1 p.Asp82Glu (c.246C>A) in the general population?

ACTC1 p.Asp82Glu (c.246C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTC1 p.Asp82Glu (c.246C>A)?

AlphaMissense predicts likely pathogenic (score 0.8473) — an in-silico prediction, not a clinical call.

ACTC1 p.Asp82Glu

c.246C>A · rs373261583 · VCV1709086

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8473 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypertrophic cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.8473	likely pathogenic
REVEL	0.656	pathogenic-leaning
SaProt	LLR -10.82	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -6	GERP -4.7
Regional constraint	o/e 0.34	constrained · MANE · 1,330 bp · p 2.8e-11 · regional, not allelic
Overall
CADD	1.082	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Asp82Glu
Coding: c.246C>A
dbSNP: rs373261583
Type: single nucleotide variant
Location: chr15:34793453 (GRCh38)

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

Disease context

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

Also linked: dilated cardiomyopathy 1R

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-asp82glu (accessed [today's date]).

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