Is CSRP3 p.Trp4Arg (c.10T>C) pathogenic?

CSRP3 p.Trp4Arg (c.10T>C) is classified Conflicting classifications of pathogenicity in CSRP3 (ClinVar, Conflicting submitters, 22 submitters; last evaluated 2026-05-01). AlphaMissense: likely pathogenic (0.9805); Rare (popmax 0.498%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with CSRP3 p.Trp4Arg (c.10T>C)?

CSRP3 p.Trp4Arg (c.10T>C) is associated with Cardiovascular phenotype, cardiomyopathy, dilated cardiomyopathy (ClinVar).

How common is CSRP3 p.Trp4Arg (c.10T>C) in the general population?

CSRP3 p.Trp4Arg (c.10T>C) is rare (popmax 0.498%, nfe) (gnomAD).

What do computational predictors say about CSRP3 p.Trp4Arg (c.10T>C)?

AlphaMissense predicts likely pathogenic (score 0.9805) — an in-silico prediction, not a clinical call.

CSRP3 p.Trp4Arg

c.10T>C · rs45550635 · VCV8776

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 22 submitters

AlphaMissense

likely pathogenic

0.9805 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.498%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.9805	likely pathogenic
REVEL	0.474	indeterminate
SaProt	LLR -11.97	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 9.2	GERP 5.7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 9,775 bp · p 0.57 · regional, not allelic
Overall
CADD	25.1	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 0.498% European (non-Finnish) · 5,879/1,179,868 alleles

Filtering AF 0.488% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.483%

Overall 0.39% 6,297/1,613,994 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.75%	57
European (non-Finnish)grpmax	0.498%	201
Remaining individualsnot grpmax-eligible	0.277%	361
Admixed American	0.107%	938
Finnishnot grpmax-eligible	0.0812%	1,231
South Asian	0.0769%	1,301
African / African-American	0.0506%	1,975
Middle Eastern	0.0495%	2,021
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,801

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Trp4Arg
Coding: c.10T>C
MANE Select: NM_003476
dbSNP: rs45550635
Type: single nucleotide variant
Location: chr11:19192439 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.91 · 2 PDB
Residue 4: a UniProt-annotated variant site (in cmd1m; uncertain significance; decreases interaction with tcap); the 'interaction with tcap' 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: cardiomyopathy dilated cardiomyopathy hypertrophic cardiomyopathy dilated cardiomyopathy 1M hypertrophic cardiomyopathy 12

Similar variants

CSRP3 p.Trp4fs Conflicting classifications of pathogenicity ★ 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-trp4arg (accessed [today's date]).

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