CRB2 p.Cys640=
c.1920C>T · rs55965026 · VCV1168664
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Common
common (popmax 7.28%, afr) — too common for a highly-penetrant pathogenic allele
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 -3 | GERP -4.5 |
| Overall | ||
| CADD | 2.282 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
7.28%
African / African-American · 5,450/74,814 alleles
Filtering AF
7.12%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 7.06%
Overall
2.91%
46,605/1,603,016 alleles · common
exomes 40,946/1,450,770 · genomes 5,659/152,246 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 7.28% | 14 |
| Amishnot grpmax-eligible | 5.6% | 18 |
| European (non-Finnish) | 3.11% | 32 |
| Remaining individualsnot grpmax-eligible | 2.56% | 39 |
| Finnishnot grpmax-eligible | 1.86% | 54 |
| South Asian | 1.19% | 84 |
| Admixed American | 1.02% | 98 |
| Middle Eastern | 0.881% | 113 |
| Ashkenazi Jewishnot grpmax-eligible | 0.283% | 354 |
| East Asian | 0.0112% | 8,942 |
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.Cys640=
- Coding
- c.1920C>T
- MANE Select
- NM_173689
- dbSNP
- rs55965026
- Type
- single nucleotide variant
- Location
- chr9:123370973 (GRCh38)
- Gene constraint
- LOEUF 1.202 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.95 · 1 PDB
- Residue 640
- the egf-like 10 domain; a disulfide bond; a UniProt-annotated variant site (in fsgs9; uncertain significance)
Similar variants
- CRB2 p.Cys640Ter Pathogenic ★ 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-cys640 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown