CRB2 p.Pro1058=
c.3174C>G · rs373493381 · VCV2146974
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0828%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -7.8 | GERP -3.8 |
| Overall | ||
| CADD | 3.316 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0828%
East Asian · 30/36,248 alleles
Filtering AF
0.0595%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0517%
Overall
0.00457%
69/1,508,980 alleles · ultra-rare
exomes 61/1,356,788 · genomes 8/152,192 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0828% | 1,208 |
| Remaining individualsnot grpmax-eligible | 0.0395% | 2,529 |
| South Asian | 0.015% | 6,652 |
| European (non-Finnish) | 0.000351% | 285,158 |
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
- CRB2
- Protein
- p.Pro1058=
- Coding
- c.3174C>G
- MANE Select
- NM_173689
- dbSNP
- rs373493381
- Type
- single nucleotide variant
- Location
- chr9:123373705 (GRCh38)
- Gene constraint
- LOEUF 1.202 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.95 · 1 PDB
- Residue 1058
- a UniProt-annotated variant site (in vmckd; uncertain significance); the egf-like 12 domain; a UniProt-annotated variant site (in fsgs9; uncertain significance)
Similar variants
- CRB2 p.Arg275Ter Pathogenic ★★ same type
- CRB2 p.Cys105Ter Pathogenic/Likely pathogenic ★★ same type
- CRB2 p.Gly1205Ser Pathogenic/Likely pathogenic ★★ ⚠ same type
- CRB2 p.Trp759Ter Pathogenic ★★ same type
- CRB2 p.Ala1042Thr Uncertain significance ★★ ⚠ same type
- CRB2 p.Ala1266Pro Uncertain significance ★★ ⚠ same type
- CRB2 p.Ala228Thr Uncertain significance ★★ ⚠ same type
- CRB2 p.Ala26Asp 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/crb2-p-pro1058 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown