CRYZ p.Ile40=
c.120C>A · rs146208357 · VCV3048884
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.452%, sas)
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 4 | GERP -1, phastCons 1 |
| Overall | ||
| CADD | 8.676 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.452%
South Asian · 402/88,998 alleles
Filtering AF
0.415%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.401%
Overall
0.0588%
946/1,607,654 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.452% | 221 |
| Middle Eastern | 0.199% | 503 |
| Remaining individualsnot grpmax-eligible | 0.0691% | 1,448 |
| European (non-Finnish) | 0.0392% | 2,551 |
| Admixed American | 0.0328% | 3,051 |
| East Asian | 0.00669% | 14,954 |
| African / African-American | 0.00536% | 18,662 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00341% | 29,348 |
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.Ile40=
- Coding
- c.120C>A
- MANE Select
- NM_001889
- dbSNP
- rs146208357
- Type
- single nucleotide variant
- Location
- chr1:74723262 (GRCh38)
- Gene constraint
- LOEUF 1.547 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.95 · 1 PDB
- Residue 40
- a β-strand
Disease context
CRYZ-related disorder
Similar variants
- CRYZ p.Gln280Arg Likely benign ⚠ same condition
- CRYZ p.Glu253= Benign same condition
- CRYZ p.Gly289= 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-ile40 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown