CRYBA4 p.Gly81=
c.243C>T · rs745630849 · VCV744680
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0493%, mid)
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 -11 | GERP -3.8 |
| Overall | ||
| CADD | 4.405 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0493%
Middle Eastern · 3/6,082 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00716%
Overall
0.00229%
37/1,613,788 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0493% | 2,027 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,620 |
| African / African-American | 0.00267% | 37,477 |
| European (non-Finnish) | 0.0022% | 45,384 |
| South Asian | 0.0022% | 45,538 |
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
- CRYBA4
- Protein
- p.Gly81=
- Coding
- c.243C>T
- MANE Select
- NM_001886
- dbSNP
- rs745630849
- Type
- single nucleotide variant
- Location
- chr22:26625565 (GRCh38)
- Gene constraint
- LOEUF 1.238 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.64 · 1 PDB
- Residue 81
- an α-helix; the beta/gamma crystallin 'greek key' 2 domain
Similar variants
- CRYBB1 p.Ser228Tyr Likely pathogenic ★★ same type
- CRYBA4 p.Ile109Val Uncertain significance ★★ ⚠ same type
- CRYBA4 p.Phe22Ser Uncertain significance ★★ ⚠ same type
- CRYBA4 p.Phe29Leu Uncertain significance ★★ ⚠ same type
- CRYBA4 p.Phe57Val Uncertain significance ★★ ⚠ same type
- CRYBB1 c.300-9T>G Uncertain significance ★★ same type
- CRYBB1 c.432+5G>C Uncertain significance ★★ same type
- CRYBB1 p.Ala98Glu 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/cryba4-p-gly81 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown