Is ACTC1 p.Pro166= (c.498C>T) pathogenic?

ACTC1 p.Pro166= (c.498C>T) is classified Likely benign in ACTC1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-15). Very rare (popmax 0.00446%, eas); Associated with hypertrophic cardiomyopathy 11.

What condition is associated with ACTC1 p.Pro166= (c.498C>T)?

ACTC1 p.Pro166= (c.498C>T) is associated with hypertrophic cardiomyopathy 11, cardiomyopathy, hypertrophic cardiomyopathy (ClinVar).

How common is ACTC1 p.Pro166= (c.498C>T) in the general population?

ACTC1 p.Pro166= (c.498C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

ACTC1 p.Pro166=

c.498C>T · rs370082904 · VCV704062

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

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 4	GERP 1.4, phastCons 1
Overall
CADD	12.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,878 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00142% 23/1,614,136 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,439
European (non-Finnish)	0.00178%	56,192

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.Pro166=
Coding: c.498C>T
dbSNP: rs370082904
Type: single nucleotide variant
Location: chr15:34792526 (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-pro166 (accessed [today's date]).

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