Is ACTC1 p.Gly44= (c.132A>C) pathogenic?

ACTC1 p.Gly44= (c.132A>C) is classified Likely benign in ACTC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-24). Very rare (popmax 0.000205%); Associated with atrial septal defect 5.

What condition is associated with ACTC1 p.Gly44= (c.132A>C)?

ACTC1 p.Gly44= (c.132A>C) is associated with atrial septal defect 5, hypertrophic cardiomyopathy 11, dilated cardiomyopathy 1R (ClinVar).

How common is ACTC1 p.Gly44= (c.132A>C) in the general population?

ACTC1 p.Gly44= (c.132A>C) is very rare (popmax 0.000205%) (gnomAD).

ACTC1 p.Gly44=

c.132A>C · rs774244503 · VCV2057989

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000205%)

Conditions

atrial septal defect 5

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 -3.4	GERP -4.7
Overall
CADD	7.308	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000205%

Overall 0.000205% 3/1,461,648 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.Gly44=
Coding: c.132A>C
MANE Select: NM_005159
dbSNP: rs774244503
Type: single nucleotide variant
Location: chr15:34793567 (GRCh38)
Gene constraint: LOEUF 0.511 · pLI 0.97 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 95.47 · 16 PDB

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

Disease context

atrial septal defect 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypertrophic cardiomyopathy 11 dilated cardiomyopathy 1R

Similar variants

ACTC1 p.Glu101Lys Pathogenic ★★★ same condition
ACTC1 p.Val56Ile Uncertain significance ★★★ ⚠ same condition
ACTC1 p.Ala297Ser Pathogenic ★★ ⚠ same condition
ACTC1 p.Gly247Asp Pathogenic/Likely pathogenic ★★ same condition
ACTC1 p.Thr128Ile Likely pathogenic ★★ same condition
ACTC1 c.455-6G>A Uncertain significance ★★ same condition
ACTC1 c.808+1G>C Uncertain significance ★★ same condition
ACTC1 c.808+3G>A 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-gly44 (accessed [today's date]).

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