CDK5RAP2 p.Ala264=
c.792T>C · VCV3683687
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, 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 1.1 | GERP -2, phastCons 0.99 |
| Overall | ||
| CADD | 7.637 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,060 alleles
Filtering AF
0.00582%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00242%
Overall
0.000274%
4/1,461,740 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,030 |
| European (non-Finnish) | 0.00017% | 589,964 |
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
- CDK5RAP2
- Protein
- p.Ala264=
- Coding
- c.792T>C
- MANE Select
- NM_018249
- Type
- single nucleotide variant
- Location
- chr9:120530011 (GRCh38)
- Gene constraint
- LOEUF 0.692 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 60.11 · 5 PDB
Similar variants
- CDK5RAP2 c.4005-1G>A Pathogenic ★★ same type
- CDK5RAP2 c.4963+1G>A Likely pathogenic ★★ same type
- CDK5RAP2 p.Arg1403Ter Pathogenic/Likely pathogenic ★★ same type
- CDK5RAP2 p.Arg1481Ter Pathogenic/Likely pathogenic ★★ same type
- CDK5RAP2 p.Arg1558Ter Pathogenic ★★ same type
- CDK5RAP2 p.Arg427Ter Pathogenic ★★ same type
- CDK5RAP2 p.Gln1301Ter Pathogenic/Likely pathogenic ★★ same type
- CDK5RAP2 p.Gln1474Ter Pathogenic ★★ 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/cdk5rap2-p-ala264 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown