Is CSRP3 p.Ala51Asp (c.152C>A) pathogenic?

CSRP3 p.Ala51Asp (c.152C>A) is classified Uncertain significance in CSRP3 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-06-16). AlphaMissense: likely pathogenic (0.9683); Very rare (popmax 0.0022%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with CSRP3 p.Ala51Asp (c.152C>A)?

CSRP3 p.Ala51Asp (c.152C>A) is associated with Cardiovascular phenotype, cardiomyopathy, dilated cardiomyopathy 1M (ClinVar).

How common is CSRP3 p.Ala51Asp (c.152C>A) in the general population?

CSRP3 p.Ala51Asp (c.152C>A) is very rare (popmax 0.0022%, nfe) (gnomAD).

What do computational predictors say about CSRP3 p.Ala51Asp (c.152C>A)?

AlphaMissense predicts likely pathogenic (score 0.9683) — an in-silico prediction, not a clinical call.

CSRP3 p.Ala51Asp

c.152C>A · rs397516853 · VCV44689

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely pathogenic

0.9683 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.9683	likely pathogenic
REVEL	0.495	indeterminate
SaProt	LLR -6.93	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 3.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 9,775 bp · p 0.57 · regional, not allelic
Overall
CADD	23.1	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 0.0022% European (non-Finnish) · 26/1,180,018 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00161% 26/1,612,748 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.Ala51Asp
Coding: c.152C>A
MANE Select: NM_003476
dbSNP: rs397516853
Type: single nucleotide variant
Location: chr11:19188265 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.91 · 2 PDB
Residue 51: the lim zinc-binding 1 domain; a β-strand

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy dilated cardiomyopathy 1M hypertrophic cardiomyopathy 12

Similar variants

CSRP3 p.Ala51Ser 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-ala51asp (accessed [today's date]).

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