Is CSRP3 p.Phe145Cys (c.434T>G) pathogenic?

CSRP3 p.Phe145Cys (c.434T>G) is classified Likely pathogenic in CSRP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-21). AlphaMissense: likely pathogenic (0.9809); Very rare (popmax 0.00333%, amr); Associated with hypertrophic cardiomyopathy.

What condition is associated with CSRP3 p.Phe145Cys (c.434T>G)?

CSRP3 p.Phe145Cys (c.434T>G) is associated with hypertrophic cardiomyopathy (ClinVar).

How common is CSRP3 p.Phe145Cys (c.434T>G) in the general population?

CSRP3 p.Phe145Cys (c.434T>G) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CSRP3 p.Phe145Cys (c.434T>G)?

AlphaMissense predicts likely pathogenic (score 0.9809) — an in-silico prediction, not a clinical call.

CSRP3 p.Phe145Cys

c.434T>G · rs759269008 · VCV974927

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9809 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypertrophic cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.9809	likely pathogenic ✓ concordant with ClinVar
REVEL	0.962	strongly pathogenic-leaning
SaProt	LLR -14.81	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
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	28.8	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 0.00333% Admixed American · 2/60,036 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000137% 2/1,461,804 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.Phe145Cys
Coding: c.434T>G
MANE Select: NM_003476
dbSNP: rs759269008
Type: single nucleotide variant
Location: chr11:19185026 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.91 · 2 PDB
Residue 145: the lim zinc-binding 2 domain; a β-strand

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

Disease context

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

Similar variants

CSRP3 p.Arg146Cys Uncertain significance ★★ ⚠ same condition
CSRP3 p.Arg146His Uncertain significance ★★ ⚠ same condition
CSRP3 p.Cys171Gly Uncertain significance ★★ ⚠ same condition
CSRP3 p.Lys69Arg Uncertain significance ★★ ⚠ same condition
CSRP3 p.Phe30Leu Uncertain significance ★★ ⚠ same condition
CSRP3 p.Arg100His Conflicting classifications of pathogenicity ★ ⚠ same condition
CSRP3 p.Arg64Leu Uncertain significance ★ ⚠ same condition
CSRP3 p.Asn26Asp Conflicting classifications of pathogenicity ★ ⚠ 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-phe145cys (accessed [today's date]).

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