Is CSRP3 p.Phe30Ser (c.89T>C) pathogenic?

CSRP3 p.Phe30Ser (c.89T>C) is classified Uncertain significance in CSRP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-30). AlphaMissense: likely pathogenic (0.9989); Very rare (popmax 0.00223%, eas).

How common is CSRP3 p.Phe30Ser (c.89T>C) in the general population?

CSRP3 p.Phe30Ser (c.89T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CSRP3 p.Phe30Ser (c.89T>C)?

AlphaMissense predicts likely pathogenic (score 0.9989) — an in-silico prediction, not a clinical call.

CSRP3 p.Phe30Ser

c.89T>C · rs1184610308 · VCV1677749

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9989 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9989	likely pathogenic · top 8% in CSRP3
REVEL	0.866	moderately pathogenic-leaning
SaProt	LLR -14.84	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	GERP 6.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 9,775 bp · p 0.57 · regional, not allelic
Overall
CADD	27.5	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 0.00223% East Asian · 1/44,886 alleles

Overall 6.84e-05% 1/1,461,818 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.Phe30Ser
Coding: c.89T>C
MANE Select: NM_003476
dbSNP: rs1184610308
Type: single nucleotide variant
Location: chr11:19192360 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.91 · 2 PDB
Residue 30: the lim zinc-binding 1 domain; a β-strand

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

Similar variants

CSRP3 p.Phe30Leu Uncertain significance ★★ ⚠ same residue
CSRP3 p.Phe30= Likely benign ★★ same residue
CSRP3 c.414+1G>T Likely pathogenic ★★ same type
CSRP3 p.Cys37Ter Pathogenic/Likely pathogenic ★★ same type
CSRP3 p.Cys58Gly Pathogenic ★★ same type
CSRP3 p.Lys113Ter Pathogenic ★★ same type
CSRP3 c.113-3C>T Uncertain significance ★★ same type
CSRP3 c.414+6A>G Uncertain significance ★★ same type

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-phe30ser (accessed [today's date]).

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