Is CSRP3 p.Pro2Gln (c.5C>A) pathogenic?

CSRP3 p.Pro2Gln (c.5C>A) is classified Uncertain significance in CSRP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-28). AlphaMissense: likely pathogenic (0.6738); Very rare (popmax 0.000254%, nfe); Associated with dilated cardiomyopathy 1M.

What condition is associated with CSRP3 p.Pro2Gln (c.5C>A)?

CSRP3 p.Pro2Gln (c.5C>A) is associated with dilated cardiomyopathy 1M, hypertrophic cardiomyopathy 12 (ClinVar).

How common is CSRP3 p.Pro2Gln (c.5C>A) in the general population?

CSRP3 p.Pro2Gln (c.5C>A) is very rare (popmax 0.000254%, nfe) (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.Pro2Gln (c.5C>A)?

AlphaMissense predicts likely pathogenic (score 0.6738) — an in-silico prediction, not a clinical call.

CSRP3 p.Pro2Gln

c.5C>A · rs762730416 · VCV2064029

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6738 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

dilated cardiomyopathy 1M

Computational evidence

Protein change
AlphaMissense	0.6738	likely pathogenic
REVEL	0.458	indeterminate
SaProt	LLR -13.80	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 6.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 9,775 bp · p 0.57 · regional, not allelic
Overall
CADD	26.3	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 0.000254% European (non-Finnish) · 3/1,179,754 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,574 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.Pro2Gln
Coding: c.5C>A
MANE Select: NM_003476
dbSNP: rs762730416
Type: single nucleotide variant
Location: chr11:19192444 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.91 · 2 PDB
Residue 2: the 'interaction with tcap' region

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.Pro2Ser 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-pro2gln (accessed [today's date]).

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