CRB2 p.Asp261=
c.783C>T · VCV4904425
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.012%, amr)
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 -2.5 | GERP -3.3 |
| Overall | ||
| CADD | 7.305 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.012%
Admixed American · 7/58,388 alleles
Filtering AF
0.00557%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00399%
Overall
0.00212%
34/1,601,012 alleles · ultra-rare
exomes 29/1,448,874 · genomes 5/152,138 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.012% | 8,341 |
| South Asian | 0.00442% | 22,609 |
| Remaining individualsnot grpmax-eligible | 0.00322% | 31,088 |
| East Asian | 0.00223% | 44,744 |
| European (non-Finnish) | 0.00161% | 62,006 |
| African / African-American | 0.00134% | 74,594 |
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.Asp261=
- Coding
- c.783C>T
- MANE Select
- NM_173689
- Type
- single nucleotide variant
- Location
- chr9:123367200 (GRCh38)
- Gene constraint
- LOEUF 1.202 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.95 · 1 PDB
- Residue 261
- the 'required for maximum inhibition of app amyloid-beta peptide secretion' region; the egf-like 6 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-asp261 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown