Is ACTC1 p.Lys217Arg (c.650A>G) pathogenic?

ACTC1 p.Lys217Arg (c.650A>G) is classified Uncertain significance in ACTC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-13). AlphaMissense: likely benign (0.2661); Absent from gnomAD v4.1; Associated with dilated cardiomyopathy 1R.

What condition is associated with ACTC1 p.Lys217Arg (c.650A>G)?

ACTC1 p.Lys217Arg (c.650A>G) is associated with dilated cardiomyopathy 1R, hypertrophic cardiomyopathy 11, atrial septal defect 5 (ClinVar).

How common is ACTC1 p.Lys217Arg (c.650A>G) in the general population?

ACTC1 p.Lys217Arg (c.650A>G) 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.Lys217Arg (c.650A>G)?

AlphaMissense predicts likely benign (score 0.2661) — an in-silico prediction, not a clinical call.

ACTC1 p.Lys217Arg

c.650A>G · VCV4783291

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2661 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dilated cardiomyopathy 1R

Computational evidence

Protein change
AlphaMissense	0.2661	likely benign
REVEL	0.782	moderately pathogenic-leaning
SaProt	LLR -12.79	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.16	constrained · MANE · 2,113 bp · p 8.3e-37 · regional, not allelic
Overall
CADD	26.2	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.Lys217Arg
Coding: c.650A>G
Type: single nucleotide variant
Location: chr15:34792248 (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-lys217arg (accessed [today's date]).

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