CRYBB2 p.Gly77=
c.231T>C · rs761853361 · VCV1093017
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.085%, amr)
Conditions
1
cataract 3 multiple types
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.49 | donor loss · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -15 | GERP -3.7 |
| Overall | ||
| CADD | 0.117 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.085%
Admixed American · 51/60,004 alleles
Filtering AF
0.0664%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0598%
Overall
0.00527%
85/1,613,934 alleles · ultra-rare
exomes 74/1,461,882 · genomes 11/152,052 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.085% | 1,177 |
| African / African-American | 0.00801% | 12,482 |
| European (non-Finnish) | 0.00229% | 43,704 |
| South Asian | 0.0011% | 91,074 |
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
- CRYBB2
- Protein
- p.Gly77=
- Coding
- c.231T>C
- MANE Select
- NM_000496
- dbSNP
- rs761853361
- Type
- single nucleotide variant
- Location
- chr22:25227910 (GRCh38)
- Gene constraint
- LOEUF 0.765 · pLI 0.09 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 89.05 · 3 PDB
- Residue 77
- a β-strand; the beta/gamma crystallin 'greek key' 2 domain
Similar variants
- CRYBB2 p.Gly77Val Likely pathogenic ★ same residue
- CRYBB2 p.Gly77Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
- CRYBB2 p.Arg188Cys Pathogenic/Likely pathogenic ★★ same condition
- CRYBB2 p.Arg188His Pathogenic ★★ same condition
- CRYBB2 p.Gln155Ter Pathogenic/Likely pathogenic ★★ same condition
- CRYBB2 p.Gly119Arg Pathogenic/Likely pathogenic ★★ same condition
- CRYBB2 p.Arg160Pro Uncertain significance ★★ ⚠ same condition
- CRYBB2 p.Gly57Glu Uncertain significance ★★ ⚠ same condition
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/crybb2-p-gly77 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown