Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Common
common (popmax 42.9%, sas) — too common for a highly-penetrant pathogenic allele
Conditions
1
cataract 3 multiple types
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 0.008 | GERP -3.7, phastCons 0.48 |
| Overall | ||
| CADD | 4.691 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
42.9%
South Asian · 39,074/91,058 alleles
Filtering AF
42.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 42.4%
Overall
23.6%
381,289/1,613,704 alleles · common
exomes 343,437/1,461,692 · genomes 37,852/152,012 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 42.9% | 2 |
| East Asian | 41.1% | 2 |
| Amishnot grpmax-eligible | 29.3% | 3 |
| Admixed American | 29.2% | 3 |
| Middle Eastern | 29.1% | 3 |
| African / African-American | 27.4% | 4 |
| Ashkenazi Jewishnot grpmax-eligible | 26.7% | 4 |
| Remaining individualsnot grpmax-eligible | 25.3% | 4 |
| European (non-Finnish) | 21% | 5 |
| Finnishnot grpmax-eligible | 18.7% | 5 |
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.Gly161=
- Coding
- c.483G>A
- MANE Select
- NM_000496
- dbSNP
- rs8140949
- Type
- single nucleotide variant
- Location
- chr22:25231637 (GRCh38)
- Gene constraint
- LOEUF 0.765 · pLI 0.09 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 89.05 · 3 PDB
- Residue 161
- a UniProt-annotated variant site (in ctrct3); a β-strand; the beta/gamma crystallin 'greek key' 4 domain
Similar variants
- CRYBB2 p.Gly161Arg Uncertain significance ★ ⚠ 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
- CRYBB2 p.Gly61Ser 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-gly161 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown