CRB2 p.Pro849=
c.2547C>T · rs201242880 · VCV732277
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
rare (popmax 0.314%, mid)
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 -1.9 | GERP -4.9 |
| Overall | ||
| CADD | 6.984 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.314%
Middle Eastern · 19/6,058 alleles
Filtering AF
0.205%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.171%
Overall
0.0414%
668/1,612,554 alleles · rare
exomes 603/1,460,204 · genomes 65/152,350 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.314% | 319 |
| Ashkenazi Jewishnot grpmax-eligible | 0.122% | 818 |
| Admixed American | 0.109% | 921 |
| Remaining individualsnot grpmax-eligible | 0.0833% | 1,201 |
| African / African-American | 0.0826% | 1,210 |
| European (non-Finnish) | 0.0354% | 2,821 |
| East Asian | 0.0245% | 4,080 |
| South Asian | 0.00551% | 18,162 |
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.Pro849=
- Coding
- c.2547C>T
- MANE Select
- NM_173689
- dbSNP
- rs201242880
- Type
- single nucleotide variant
- Location
- chr9:123372287 (GRCh38)
- Gene constraint
- LOEUF 1.202 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.95 · 1 PDB
- Residue 849
- a UniProt-annotated variant site (in vmckd; uncertain significance); 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-pro849 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown