CRY1 p.Ala331=
c.993G>A · rs139335342 · VCV729183
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.408%, 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 -1.4 | GERP -4.3 |
| Overall | ||
| CADD | 9.006 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.408%
African / African-American · 306/75,072 alleles
Filtering AF
0.37%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.355%
Overall
0.0218%
352/1,614,240 alleles · rare
exomes 174/1,461,892 · genomes 178/152,348 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.408% | 245 |
| Middle Eastern | 0.033% | 3,031 |
| Remaining individualsnot grpmax-eligible | 0.0192% | 5,209 |
| Admixed American | 0.015% | 6,670 |
| South Asian | 0.00549% | 18,218 |
| European (non-Finnish) | 0.00153% | 65,558 |
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
- CRY1
- Protein
- p.Ala331=
- Coding
- c.993G>A
- MANE Select
- NM_004075
- dbSNP
- rs139335342
- Type
- single nucleotide variant
- Location
- chr12:106999695 (GRCh38)
- Gene constraint
- LOEUF 0.733 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.32
Similar variants
- CRY1 p.Ala331Gly Uncertain significance ★ same residue
- CRY1 p.Arg256Gln Uncertain significance ★★ ⚠ same type
- CRY1 p.Thr179Ala Uncertain significance ★★ ⚠ same type
- CRY1 p.Ala501= Benign ★★ same type
- CRY1 p.Ala111Thr Uncertain significance ★ ⚠ same type
- CRY1 p.Ala241Val Uncertain significance ★ ⚠ same type
- CRY1 p.Ala5Gly Uncertain significance ★ ⚠ same type
- CRY1 p.Arg14Gln 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/cry1-p-ala331 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown