Is CSRP3 p.Cys61Arg (c.181T>C) pathogenic?

CSRP3 p.Cys61Arg (c.181T>C) is classified Uncertain significance in CSRP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-02-25). AlphaMissense: likely pathogenic (0.9996); Absent from gnomAD v4.1; Associated with hypertrophic cardiomyopathy 12.

What condition is associated with CSRP3 p.Cys61Arg (c.181T>C)?

CSRP3 p.Cys61Arg (c.181T>C) is associated with hypertrophic cardiomyopathy 12, dilated cardiomyopathy 1M (ClinVar).

How common is CSRP3 p.Cys61Arg (c.181T>C) in the general population?

CSRP3 p.Cys61Arg (c.181T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CSRP3 p.Cys61Arg (c.181T>C)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

CSRP3 p.Cys61Arg

c.181T>C · rs866941870 · VCV582911

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypertrophic cardiomyopathy 12

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic · top 2% in CSRP3
REVEL	0.889	moderately pathogenic-leaning
SaProt	LLR -16.72	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.75 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 6.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 9,775 bp · p 0.57 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CSRP3
Protein: p.Cys61Arg
Coding: c.181T>C
MANE Select: NM_003476
dbSNP: rs866941870
Type: single nucleotide variant
Location: chr11:19188236 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.91 · 2 PDB
Residue 61: the lim zinc-binding 1 domain; an α-helix

Full CSRP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hypertrophic cardiomyopathy 12 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dilated cardiomyopathy 1M

Similar variants

CSRP3 p.Cys61Tyr Uncertain significance ★ ⚠ same residue
CSRP3 c.414+1G>T Likely pathogenic ★★ same condition
CSRP3 p.Cys37Ter Pathogenic/Likely pathogenic ★★ same condition
CSRP3 p.Cys58Gly Pathogenic ★★ same condition
CSRP3 p.Lys113Ter Pathogenic ★★ same condition
CSRP3 c.113-3C>T Uncertain significance ★★ same condition
CSRP3 c.414+6A>G Uncertain significance ★★ same condition
CSRP3 c.415-1G>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/csrp3-p-cys61arg (accessed [today's date]).

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