Is ACTC1 p.Leu348= (c.1044G>A) pathogenic?

ACTC1 p.Leu348= (c.1044G>A) is classified Likely benign in ACTC1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-12-21). Very rare (popmax 0.000254%, nfe); Associated with hypertrophic cardiomyopathy 11.

What condition is associated with ACTC1 p.Leu348= (c.1044G>A)?

ACTC1 p.Leu348= (c.1044G>A) is associated with hypertrophic cardiomyopathy 11, cardiomyopathy, hypertrophic cardiomyopathy (ClinVar).

How common is ACTC1 p.Leu348= (c.1044G>A) in the general population?

ACTC1 p.Leu348= (c.1044G>A) is very rare (popmax 0.000254%, nfe) (gnomAD).

ACTC1 p.Leu348=

c.1044G>A · rs1461497941 · VCV1171045

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

hypertrophic cardiomyopathy 11

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 1.5	GERP 2.3, phastCons 1
Overall
CADD	10.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,030 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,986 alleles · very rare

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.Leu348=
Coding: c.1044G>A
dbSNP: rs1461497941
Type: single nucleotide variant
Location: chr15:34790502 (GRCh38)

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

Disease context

hypertrophic cardiomyopathy 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy hypertrophic cardiomyopathy 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-leu348 (accessed [today's date]).

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