Is CSRP3 p.Cys58= (c.174C>T) pathogenic?

CSRP3 p.Cys58= (c.174C>T) is classified Likely benign in CSRP3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-03). Very rare (popmax 0.0011%, sas); Associated with hypertrophic cardiomyopathy 12.

What condition is associated with CSRP3 p.Cys58= (c.174C>T)?

CSRP3 p.Cys58= (c.174C>T) is associated with hypertrophic cardiomyopathy 12, dilated cardiomyopathy 1M (ClinVar).

How common is CSRP3 p.Cys58= (c.174C>T) in the general population?

CSRP3 p.Cys58= (c.174C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

CSRP3 p.Cys58=

c.174C>T · rs1057520959 · VCV381101

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

hypertrophic cardiomyopathy 12

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 0.83	GERP -5.5, phastCons 0.97
Overall
CADD	1.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,036 alleles

Overall 6.84e-05% 1/1,461,116 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: CSRP3
Protein: p.Cys58=
Coding: c.174C>T
MANE Select: NM_003476
dbSNP: rs1057520959
Type: single nucleotide variant
Location: chr11:19188243 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.91 · 2 PDB
Residue 58: the lim zinc-binding 1 domain; a UniProt-annotated variant site (in cmh12; decreases interaction with nrap and actn2, decreases zinc-binding and impairs protein stability, decreases pkc/prkca activity)

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.Cys58Gly Pathogenic ★★ same residue
CSRP3 c.414+1G>T Likely pathogenic ★★ same condition
CSRP3 p.Cys37Ter Pathogenic/Likely 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
CSRP3 c.*159C>T 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-cys58 (accessed [today's date]).

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