Is ACTC1 p.Ala21Val (c.62C>T) pathogenic?

ACTC1 p.Ala21Val (c.62C>T) is classified Conflicting classifications of pathogenicity in ACTC1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-02-01). AlphaMissense: likely pathogenic (0.8936); Absent from gnomAD v4.1; Associated with ACTC1-related disorder.

What condition is associated with ACTC1 p.Ala21Val (c.62C>T)?

ACTC1 p.Ala21Val (c.62C>T) is associated with ACTC1-related disorder, hypertrophic cardiomyopathy 11, atrial septal defect 5 (ClinVar).

How common is ACTC1 p.Ala21Val (c.62C>T) in the general population?

ACTC1 p.Ala21Val (c.62C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTC1 p.Ala21Val (c.62C>T)?

AlphaMissense predicts likely pathogenic (score 0.8936) — an in-silico prediction, not a clinical call.

ACTC1 p.Ala21Val

c.62C>T · rs1060502823 · VCV410264

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8936 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ACTC1-related disorder

Computational evidence

Protein change
AlphaMissense	0.8936	likely pathogenic
REVEL	0.876	moderately pathogenic-leaning
SaProt	LLR -13.66	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.06	constrained · MANE · 60 bp · p 1.9e-07 · regional, not allelic
Overall
CADD	31.0	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.Ala21Val
Coding: c.62C>T
dbSNP: rs1060502823
Type: single nucleotide variant
Location: chr15:34794747 (GRCh38)

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

Disease context

ACTC1-related disorder

Also linked: hypertrophic cardiomyopathy 11 atrial septal defect 5 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-ala21val (accessed [today's date]).

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