CRB2 p.Pro1280=
c.3840G>A · rs139686085 · VCV745958
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.088%, 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 -20 | GERP -4.6 |
| Overall | ||
| CADD | 0.007 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.088%
East Asian · 39/44,320 alleles
Filtering AF
0.0661%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0585%
Overall
0.00907%
144/1,588,472 alleles · ultra-rare
exomes 112/1,436,162 · genomes 32/152,310 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.088% | 1,136 |
| African / African-American | 0.0604% | 1,657 |
| Middle Eastern | 0.0335% | 2,981 |
| Remaining individualsnot grpmax-eligible | 0.00651% | 15,353 |
| South Asian | 0.0046% | 21,729 |
| European (non-Finnish) | 0.00403% | 24,818 |
| Admixed American | 0.00347% | 28,819 |
| Finnishnot grpmax-eligible | 0.00161% | 62,046 |
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.Pro1280=
- Coding
- c.3840G>A
- MANE Select
- NM_173689
- dbSNP
- rs139686085
- Type
- single nucleotide variant
- Location
- chr9:123377044 (GRCh38)
- Gene constraint
- LOEUF 1.202 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.95 · 1 PDB
- Residue 1280
- a UniProt-annotated variant site (in vmckd; uncertain significance); the 'interaction with epb41l5' region; a UniProt-annotated variant site (in fsgs9; uncertain significance)
Similar variants
- CRB2 p.Pro1280Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- 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
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-pro1280 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown