Is ACTC1 p.Lys63Arg (c.188A>G) pathogenic?

ACTC1 p.Lys63Arg (c.188A>G) is classified Uncertain significance in ACTC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-07-31). AlphaMissense: ambiguous (0.5054); Absent from gnomAD v4.1; Associated with atrial septal defect 5.

What condition is associated with ACTC1 p.Lys63Arg (c.188A>G)?

ACTC1 p.Lys63Arg (c.188A>G) is associated with atrial septal defect 5, hypertrophic cardiomyopathy 11, dilated cardiomyopathy 1R (ClinVar).

How common is ACTC1 p.Lys63Arg (c.188A>G) in the general population?

ACTC1 p.Lys63Arg (c.188A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTC1 p.Lys63Arg (c.188A>G)?

AlphaMissense predicts ambiguous (score 0.5054) — an in-silico prediction, not a clinical call.

ACTC1 p.Lys63Arg

c.188A>G · rs794727502 · VCV196406

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5054 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

atrial septal defect 5

Computational evidence

Protein change
AlphaMissense	0.5054	ambiguous
REVEL	0.798	moderately pathogenic-leaning
SaProt	LLR -10.64	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.2	GERP 2.3, phastCons 1
Regional constraint	o/e 0.34	constrained · MANE · 1,330 bp · p 2.8e-11 · regional, not allelic
Overall
CADD	29.2	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.Lys63Arg
Coding: c.188A>G
dbSNP: rs794727502
Type: single nucleotide variant
Location: chr15:34793511 (GRCh38)

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

Disease context

atrial septal defect 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypertrophic cardiomyopathy 11 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-lys63arg (accessed [today's date]).

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