CRYZ p.Glu253=
c.759A>G · rs17552114 · VCV3057215
Benign
No assertion criteria
Classification
Benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 4.79%, nfe)
Conditions
1
CRYZ-related disorder
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 0.64 | GERP -3, phastCons 1 |
| Overall | ||
| CADD | 6.643 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.79%
European (non-Finnish) · 56,496/1,178,842 alleles
Filtering AF
4.76%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.75%
Overall
4.01%
64,730/1,612,554 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 4.79% | 21 |
| Remaining individualsnot grpmax-eligible | 3.73% | 27 |
| Ashkenazi Jewishnot grpmax-eligible | 3.51% | 28 |
| Middle Eastern | 2.49% | 40 |
| Admixed American | 2.49% | 40 |
| Finnishnot grpmax-eligible | 1.89% | 53 |
| Amishnot grpmax-eligible | 1.75% | 57 |
| South Asian | 1.35% | 74 |
| African / African-American | 1.03% | 97 |
| East Asian | 0.00892% | 11,209 |
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
- CRYZ
- Protein
- p.Glu253=
- Coding
- c.759A>G
- MANE Select
- NM_001889
- dbSNP
- rs17552114
- Type
- single nucleotide variant
- Location
- chr1:74706968 (GRCh38)
- Gene constraint
- LOEUF 1.547 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.95 · 1 PDB
- Residue 253
- a β-strand
Disease context
CRYZ-related disorder
Similar variants
- CRYZ p.Gln280Arg Likely benign same condition
- CRYZ p.Gly289= Likely benign same condition
- CRYZ p.Ile40= Likely benign same condition
- CRYZ p.Tyr205= Benign same condition
- CRYZ c.265-1G>A Likely benign ★★ same type
- CRYZ p.Glu183Lys Benign ★★ same type
- CRYZ p.Ala139Thr Uncertain significance ★ same type
- CRYZ p.Ala148Val 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/cryz-p-glu253 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown