Is CSRP3 p.Pro96fs (c.286_287del) pathogenic?

CSRP3 p.Pro96fs (c.286287del) is classified Conflicting classifications of pathogenicity in CSRP3 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-12-12). Very rare (popmax 0.00267%, afr); Associated with Cardiovascular phenotype.

What condition is associated with CSRP3 p.Pro96fs (c.286_287del)?

CSRP3 p.Pro96fs (c.286_287del) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1M, hypertrophic cardiomyopathy 12 (ClinVar).

How common is CSRP3 p.Pro96fs (c.286_287del) in the general population?

CSRP3 p.Pro96fs (c.286_287del) is very rare (popmax 0.00267%, afr) (gnomAD).

CSRP3 p.Pro96fs

c.286_287del · rs960577385 · VCV1284733

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.39	phastCons 0.23
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,932 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.00062% 10/1,614,066 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,466
European (non-Finnish)	0.000678%	147,504

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.Pro96fs
Coding: c.286_287del
MANE Select: NM_003476
dbSNP: rs960577385
Type: Deletion
Location: chr11:19186343 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.91 · 2 PDB
Residue 96: the 'interaction with clf2 and isoform 2' region

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: dilated cardiomyopathy 1M hypertrophic cardiomyopathy 12

Similar variants

CSRP3 p.Pro96Leu Uncertain significance ★★ ⚠ same residue
CSRP3 p.Pro96Ser Uncertain significance ★★ ⚠ same residue
CSRP3 p.Lys192fs Uncertain significance ★★ same condition
CSRP3 p.Arg100fs Pathogenic ★ same condition
CSRP3 p.Arg28fs Pathogenic ★ same condition
CSRP3 p.Gln93fs Pathogenic ★ same condition
CSRP3 p.His19fs Pathogenic ★ same condition
CSRP3 p.Ile56fs Pathogenic ★ 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-pro96fs (accessed [today's date]).

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