Is CSRP3 p.Ala129Ser (c.385G>T) pathogenic?

CSRP3 p.Ala129Ser (c.385G>T) is classified Uncertain significance in CSRP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-25). AlphaMissense: likely benign (0.2396); Absent from gnomAD v4.1; Associated with hypertrophic cardiomyopathy 12.

What condition is associated with CSRP3 p.Ala129Ser (c.385G>T)?

CSRP3 p.Ala129Ser (c.385G>T) is associated with hypertrophic cardiomyopathy 12, dilated cardiomyopathy 1M (ClinVar).

How common is CSRP3 p.Ala129Ser (c.385G>T) in the general population?

CSRP3 p.Ala129Ser (c.385G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CSRP3 p.Ala129Ser (c.385G>T)?

AlphaMissense predicts likely benign (score 0.2396) — an in-silico prediction, not a clinical call.

CSRP3 p.Ala129Ser

c.385G>T · rs2494220237 · VCV2936215

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2396 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hypertrophic cardiomyopathy 12

Computational evidence

Protein change
AlphaMissense	0.2396	likely benign
REVEL	0.478	indeterminate
SaProt	LLR -10.42	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 9,775 bp · p 0.57 · regional, not allelic
Overall
CADD	26.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CSRP3
Protein: p.Ala129Ser
Coding: c.385G>T
MANE Select: NM_003476
dbSNP: rs2494220237
Type: single nucleotide variant
Location: chr11:19186245 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.91 · 2 PDB
Residue 129: the lim zinc-binding 2 domain; a turn

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.Ala129Gly Uncertain significance ★ ⚠ same residue
CSRP3 p.Ala129Val 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

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-ala129ser (accessed [today's date]).

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