Is ACTC1 p.Arg185Trp (c.553C>T) pathogenic?

ACTC1 p.Arg185Trp (c.553C>T) is classified Likely pathogenic in ACTC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2016-11-03). AlphaMissense: likely pathogenic (0.9879); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with ACTC1 p.Arg185Trp (c.553C>T)?

ACTC1 p.Arg185Trp (c.553C>T) is associated with Inborn genetic diseases, dilated cardiomyopathy (ClinVar).

How common is ACTC1 p.Arg185Trp (c.553C>T) in the general population?

ACTC1 p.Arg185Trp (c.553C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about ACTC1 p.Arg185Trp (c.553C>T)?

AlphaMissense predicts likely pathogenic (score 0.9879) — an in-silico prediction, not a clinical call.

ACTC1 p.Arg185Trp

c.553C>T · rs397517065 · VCV45183

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9879 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9879	likely pathogenic ✓ concordant with ClinVar
REVEL	0.937	strongly pathogenic-leaning
SaProt	LLR -15.94	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.3	GERP 1.4, phastCons 1
Regional constraint	o/e 0.16	constrained · MANE · 2,113 bp · p 8.3e-37 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,072 alleles

Overall 0.000657% 1/152,196 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.Arg185Trp
Coding: c.553C>T
dbSNP: rs397517065
Type: single nucleotide variant
Location: chr15:34792471 (GRCh38)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dilated cardiomyopathy

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-arg185trp (accessed [today's date]).

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