Is CSRP3 p.Cys120Phe (c.359G>T) pathogenic?

CSRP3 p.Cys120Phe (c.359G>T) is classified Uncertain significance in CSRP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-16). AlphaMissense: likely pathogenic (0.9974); Very rare (popmax 0.00223%, eas); Associated with dilated cardiomyopathy 1M.

What condition is associated with CSRP3 p.Cys120Phe (c.359G>T)?

CSRP3 p.Cys120Phe (c.359G>T) is associated with dilated cardiomyopathy 1M, hypertrophic cardiomyopathy 12 (ClinVar).

How common is CSRP3 p.Cys120Phe (c.359G>T) in the general population?

CSRP3 p.Cys120Phe (c.359G>T) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Familial isolated dilated cardiomyopathy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CSRP3 p.Cys120Phe (c.359G>T)?

AlphaMissense predicts likely pathogenic (score 0.9974) — an in-silico prediction, not a clinical call.

CSRP3 p.Cys120Phe

c.359G>T · VCV4794380

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9974 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dilated cardiomyopathy 1M

Computational evidence

Protein change
AlphaMissense	0.9974	likely pathogenic · top 10% in CSRP3
REVEL	0.972	strongly pathogenic-leaning
SaProt	LLR -15.31	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 9,775 bp · p 0.57 · regional, not allelic
Overall
CADD	27.9	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

Grpmax group 0.00223% East Asian · 1/44,888 alleles

Overall 0.000137% 2/1,461,888 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,888
European (non-Finnish)	8.47e-05%	1,180,030

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.Cys120Phe
Coding: c.359G>T
MANE Select: NM_003476
Type: single nucleotide variant
Location: chr11:19186271 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.91 · 2 PDB
Residue 120: the lim zinc-binding 2 domain

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

Disease context

dilated cardiomyopathy 1M — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypertrophic cardiomyopathy 12

For Familial isolated dilated cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

CSRP3 p.Cys120Arg Uncertain significance ★★ ⚠ same residue
CSRP3 p.Cys120= Likely benign ★ same residue
CSRP3 p.Cys120Tyr 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

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-cys120phe (accessed [today's date]).

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