Is ACTC1 p.Gln43= (c.129G>A) pathogenic?

ACTC1 p.Gln43= (c.129G>A) is classified Uncertain significance in ACTC1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-04). Very rare (popmax 0.00017%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with ACTC1 p.Gln43= (c.129G>A)?

ACTC1 p.Gln43= (c.129G>A) is associated with Cardiovascular phenotype, cardiomyopathy, hypertrophic cardiomyopathy (ClinVar).

How common is ACTC1 p.Gln43= (c.129G>A) in the general population?

ACTC1 p.Gln43= (c.129G>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

ACTC1 p.Gln43=

c.129G>A · rs878854753 · VCV240098

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

Cardiovascular phenotype

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

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
Pangolin	Δ0.43	loss · gain 0.01 · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,178,700 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,611,320 alleles · very rare exomes 0/1,459,104 · genomes 2/152,216 · joint denominator

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.Gln43=
Coding: c.129G>A
MANE Select: NM_005159
dbSNP: rs878854753
Type: single nucleotide variant
Location: chr15:34794680 (GRCh38)

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

Disease context

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

Also linked: cardiomyopathy 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-gln43 (accessed [today's date]).

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