CRIPT p.Ala45=
c.135A>C · VCV3705967
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, 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 3.5 | GERP -0.88, phastCons 1 |
| Overall | ||
| CADD | 13.29 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,068 alleles
Filtering AF
0.00103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000831%
Overall
0.00137%
22/1,610,686 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,068 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,170 |
| European (non-Finnish) | 0.00161% | 62,002 |
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
- CRIPT
- Protein
- p.Ala45=
- Coding
- c.135A>C
- MANE Select
- NM_014171
- Type
- single nucleotide variant
- Location
- chr2:46619679 (GRCh38)
- Gene constraint
- LOEUF 1.852 · pLI 0.19 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 78.77 · 1 PDB
Similar variants
- CRIPT p.Ala45Pro Uncertain significance ★★ ⚠ same residue
- CRIPT p.Ala45Thr Uncertain significance ★ ⚠ same residue
- CRIPT p.Ala45fs Pathogenic same residue
- CRIPT c.83-1G>A Likely pathogenic ★★ same type
- CRIPT p.Ala84Val Uncertain significance ★★ ⚠ same type
- CRIPT p.Cys86Phe Uncertain significance ★★ ⚠ same type
- CRIPT p.Gln74Arg Uncertain significance ★★ ⚠ same type
- CRIPT p.Gly81Val 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/cript-p-ala45 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown