Is CSRP3 p.Ala112Val (c.335C>T) pathogenic?

CSRP3 p.Ala112Val (c.335C>T) is classified Conflicting classifications of pathogenicity in CSRP3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-25). AlphaMissense: likely benign (0.0875); Very rare (popmax 0.00305%, nfe); Associated with hypertrophic cardiomyopathy 12.

What condition is associated with CSRP3 p.Ala112Val (c.335C>T)?

CSRP3 p.Ala112Val (c.335C>T) is associated with hypertrophic cardiomyopathy 12, dilated cardiomyopathy 1M (ClinVar).

How common is CSRP3 p.Ala112Val (c.335C>T) in the general population?

CSRP3 p.Ala112Val (c.335C>T) is very rare (popmax 0.00305%, nfe) (gnomAD).

What do computational predictors say about CSRP3 p.Ala112Val (c.335C>T)?

AlphaMissense predicts likely benign (score 0.0875) — an in-silico prediction, not a clinical call.

CSRP3 p.Ala112Val

c.335C>T · rs753711278 · VCV1058043

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0875 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00305%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypertrophic cardiomyopathy 12

Computational evidence

Protein change
AlphaMissense	0.0875	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -7.21	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 9,775 bp · p 0.57 · regional, not allelic
Overall
CADD	24.7	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 0.00305% European (non-Finnish) · 36/1,180,020 alleles

Filtering AF 0.00223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00198%

Overall 0.00248% 40/1,614,052 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00305%	32,778
African / African-American	0.00267%	37,458
Remaining individualsnot grpmax-eligible	0.0016%	62,488
South Asian	0.0011%	91,086

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.Ala112Val
Coding: c.335C>T
MANE Select: NM_003476
dbSNP: rs753711278
Type: single nucleotide variant
Location: chr11:19186295 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.91 · 2 PDB

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

Disease context

hypertrophic cardiomyopathy 12 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dilated cardiomyopathy 1M

Similar variants

CSRP3 p.Ala112Glu Uncertain significance ★★ ⚠ same residue
CSRP3 p.Ala112= Benign ★★ same residue
CSRP3 p.Ala112Gly Uncertain significance ★ ⚠ same residue
CSRP3 p.Ala112Pro 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

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-ala112val (accessed [today's date]).

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