Is ACTC1 p.Arg185= (c.555G>A) pathogenic?

ACTC1 p.Arg185= (c.555G>A) is classified Likely benign in ACTC1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-03). Ultra-rare (popmax 0.0134%, eas); Associated with cardiomyopathy.

What condition is associated with ACTC1 p.Arg185= (c.555G>A)?

ACTC1 p.Arg185= (c.555G>A) is associated with cardiomyopathy, hypertrophic cardiomyopathy 11, atrial septal defect 5 (ClinVar).

How common is ACTC1 p.Arg185= (c.555G>A) in the general population?

ACTC1 p.Arg185= (c.555G>A) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

ACTC1 p.Arg185=

c.555G>A · rs1161290776 · VCV2774924

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Conditions

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 0.62	GERP -2, phastCons 1
Overall
CADD	12.42	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,872 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000372% 6/1,614,060 alleles · ultra-rare exomes 5/1,461,894 · genomes 1/152,166 · 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.Arg185=
Coding: c.555G>A
MANE Select: NM_005159
dbSNP: rs1161290776
Type: single nucleotide variant
Location: chr15:34792469 (GRCh38)
Gene constraint: LOEUF 0.511 · pLI 0.97 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 95.47 · 16 PDB
Residue 185: an α-helix

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 11 atrial septal defect 5 dilated cardiomyopathy 1R

Similar variants

ACTC1 p.Arg185Gln Uncertain significance ★★ ⚠ same residue
ACTC1 p.Arg185Leu Uncertain significance ★ same residue
ACTC1 p.Arg185Gly Likely pathogenic ★ same residue
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

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-arg185 (accessed [today's date]).

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