Is ACTC1 p.Leu218= (c.652C>T) pathogenic?

ACTC1 p.Leu218= (c.652C>T) is classified Likely benign in ACTC1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-27). Ultra-rare (popmax 0.0267%, amr); Associated with cardiomyopathy.

How common is ACTC1 p.Leu218= (c.652C>T) in the general population?

ACTC1 p.Leu218= (c.652C>T) is ultra-rare (popmax 0.0267%, amr) (gnomAD).

ACTC1 p.Leu218=

Q: What condition is associated with ACTC1 p.Leu218= (c.652C>T)?

ACTC1 p.Leu218= (c.652C>T) is associated with cardiomyopathy, hypertrophic cardiomyopathy, hypertrophic cardiomyopathy 11 (ClinVar).

c.652C>T · rs760269526 · VCV919733

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, amr)

Conditions

cardiomyopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.7	GERP 1.4, phastCons 1
Overall
CADD	9.305	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% Admixed American · 16/60,010 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00112% 18/1,614,120 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0267%	3,751
African / African-American	0.00133%	74,942
European (non-Finnish)	8.47e-05%	1,180,057

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ACTC1
Protein: p.Leu218=
Coding: c.652C>T
dbSNP: rs760269526
Type: single nucleotide variant
Location: chr15:34792246 (GRCh38)

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

Disease context

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

Also linked: hypertrophic cardiomyopathy 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-leu218 (accessed [today's date]).

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