Is CSRP3 p.Cys171Arg (c.511T>C) pathogenic?

CSRP3 p.Cys171Arg (c.511T>C) is classified Uncertain significance in CSRP3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-24). AlphaMissense: likely pathogenic (0.9994); Very rare (popmax 0.000509%, nfe); Associated with hypertrophic cardiomyopathy 12.

What condition is associated with CSRP3 p.Cys171Arg (c.511T>C)?

CSRP3 p.Cys171Arg (c.511T>C) is associated with hypertrophic cardiomyopathy 12, dilated cardiomyopathy 1M (ClinVar).

How common is CSRP3 p.Cys171Arg (c.511T>C) in the general population?

CSRP3 p.Cys171Arg (c.511T>C) is very rare (popmax 0.000509%, nfe) (gnomAD).

What do computational predictors say about CSRP3 p.Cys171Arg (c.511T>C)?

AlphaMissense predicts likely pathogenic (score 0.9994) — an in-silico prediction, not a clinical call.

CSRP3 p.Cys171Arg

c.511T>C · rs770760020 · VCV1745475

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9994 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypertrophic cardiomyopathy 12

Computational evidence

Protein change
AlphaMissense	0.9994	likely pathogenic · top 2% in CSRP3
REVEL	0.947	strongly pathogenic-leaning
SaProt	LLR -15.90	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 9,775 bp · p 0.57 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000509% European (non-Finnish) · 6/1,178,420 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,612,322 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.Cys171Arg
Coding: c.511T>C
MANE Select: NM_003476
dbSNP: rs770760020
Type: single nucleotide variant
Location: chr11:19182744 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.91 · 2 PDB
Residue 171: the lim zinc-binding 2 domain; an α-helix

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.Cys171= Likely benign ★★ same residue
CSRP3 p.Cys171Tyr Uncertain significance ★ ⚠ same residue
CSRP3 p.Cys171Gly 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

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-cys171arg (accessed [today's date]).

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