CRYZ p.Leu305=
c.913T>C · rs147597121 · VCV728063
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.423%, afr)
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 -0.44 | GERP -4.2 |
| Overall | ||
| CADD | 0.266 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.423%
African / African-American · 317/74,996 alleles
Filtering AF
0.384%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.369%
Overall
0.0244%
394/1,612,646 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.423% | 237 |
| Remaining individualsnot grpmax-eligible | 0.04% | 2,498 |
| Admixed American | 0.0384% | 2,604 |
| South Asian | 0.022% | 4,549 |
| European (non-Finnish) | 0.000763% | 130,992 |
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.Leu305=
- Coding
- c.913T>C
- MANE Select
- NM_001889
- dbSNP
- rs147597121
- Type
- single nucleotide variant
- Location
- chr1:74706373 (GRCh38)
- Gene constraint
- LOEUF 1.547 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.95 · 1 PDB
- Residue 305
- an α-helix
Similar variants
- 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
- CRYZ p.Ala164Thr Uncertain significance ★ ⚠ same type
- CRYZ p.Ala2Pro Uncertain significance ★ ⚠ same type
- CRYZ p.Arg138Gln Uncertain significance ★ ⚠ same type
- CRYZ p.Arg138Gly 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-leu305 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown