CRB2 p.Cys47=
c.141C>T · rs138658467 · VCV3040927
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0415%, afr)
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 -13 | GERP -5.3 |
| Overall | ||
| CADD | 0.248 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0415%
African / African-American · 31/74,770 alleles
Filtering AF
0.03%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0261%
Overall
0.00375%
60/1,598,040 alleles · ultra-rare
exomes 34/1,445,726 · genomes 26/152,314 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0415% | 2,412 |
| Admixed American | 0.0067% | 14,932 |
| Remaining individualsnot grpmax-eligible | 0.00486% | 20,559 |
| East Asian | 0.00225% | 44,392 |
| European (non-Finnish) | 0.0018% | 55,593 |
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.Cys47=
- Coding
- c.141C>T
- MANE Select
- NM_173689
- dbSNP
- rs138658467
- Type
- single nucleotide variant
- Location
- chr9:123362911 (GRCh38)
- Gene constraint
- LOEUF 1.202 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.95 · 1 PDB
- Residue 47
- the 'required for maximum inhibition of app amyloid-beta peptide secretion' region
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-cys47 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown