CRB2 p.Pro433=
c.1299G>A · rs150981911 · VCV1651739
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.01%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.17 | GERP -1.9, phastCons 0.001 |
| Overall | ||
| CADD | 8.884 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.01%
Admixed American · 6/60,024 alleles
Filtering AF
0.00428%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00295%
Overall
0.00248%
40/1,613,810 alleles · very rare
exomes 33/1,461,506 · genomes 7/152,304 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.01% | 10,004 |
| African / African-American | 0.00666% | 15,008 |
| South Asian | 0.00549% | 18,216 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,837 |
| East Asian | 0.00446% | 22,443 |
| European (non-Finnish) | 0.00161% | 62,106 |
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.Pro433=
- Coding
- c.1299G>A
- MANE Select
- NM_173689
- dbSNP
- rs150981911
- Type
- single nucleotide variant
- Location
- chr9:123370352 (GRCh38)
- Gene constraint
- LOEUF 1.202 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.95 · 1 PDB
- Residue 433
- the egf-like 9 domain; the laminin g-like 1 domain; a UniProt-annotated variant site (in fsgs9; uncertain significance)
Similar variants
- CRB2 p.Pro433Leu 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-pro433 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown