Is ACTC1 p.Val341= (c.1023C>A) pathogenic?

ACTC1 p.Val341= (c.1023C>A) is classified Likely benign in ACTC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-16). Very rare (popmax 8.47e-05%, nfe); Associated with hypertrophic cardiomyopathy.

What condition is associated with ACTC1 p.Val341= (c.1023C>A)?

ACTC1 p.Val341= (c.1023C>A) is associated with hypertrophic cardiomyopathy (ClinVar).

How common is ACTC1 p.Val341= (c.1023C>A) in the general population?

ACTC1 p.Val341= (c.1023C>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

ACTC1 p.Val341=

c.1023C>A · rs1175020886 · VCV3071212

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

hypertrophic cardiomyopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.048	GERP -4.7, phastCons 0.55
Overall
CADD	3.338	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,998 alleles

Overall 6.84e-05% 1/1,461,834 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.Val341=
Coding: c.1023C>A
MANE Select: NM_005159
dbSNP: rs1175020886
Type: single nucleotide variant
Location: chr15:34790523 (GRCh38)
Gene constraint: LOEUF 0.511 · pLI 0.97 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 95.47 · 16 PDB
Residue 341: an α-helix

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

Disease context

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

Similar variants

ACTC1 p.Val341Leu Uncertain significance ★ ⚠ same residue
ACTC1 p.Glu101Lys Pathogenic ★★★ same condition
ACTC1 p.Gly345Val Uncertain significance ★★★ ⚠ same condition
ACTC1 p.Pro266Leu Uncertain significance ★★★ ⚠ same condition
ACTC1 p.Val56Ile Uncertain significance ★★★ ⚠ same condition
ACTC1 c.-12A>G Uncertain significance ★★ same condition
ACTC1 c.-1G>A Uncertain significance ★★ same condition
ACTC1 p.Ala60Thr Uncertain significance ★★ ⚠ same condition

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-val341 (accessed [today's date]).

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