CDK5RAP2 p.Glu1683=
c.5049G>A · rs886063392 · VCV364752
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000169%, nfe)
Conditions
1
microcephaly 3, primary, autosomal recessive
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 1.8 | GERP -0.13, phastCons 0.97 |
| Overall | ||
| CADD | 6.328 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000169%
European (non-Finnish) · 2/1,180,020 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000137%
2/1,461,840 alleles · very rare
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.Glu1683=
- Coding
- c.5049G>A
- MANE Select
- NM_018249
- dbSNP
- rs886063392
- Type
- single nucleotide variant
- Location
- chr9:120403064 (GRCh38)
- Gene constraint
- LOEUF 0.692 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 60.11 · 5 PDB
- Residue 1683
- the 'disordered' region
Similar variants
- CDK5RAP2 c.4005-1G>A Pathogenic ★★ same condition
- CDK5RAP2 c.4963+1G>A Likely pathogenic ★★ same condition
- CDK5RAP2 p.Arg1403Ter Pathogenic/Likely pathogenic ★★ same condition
- CDK5RAP2 p.Arg1481Ter Pathogenic/Likely pathogenic ★★ same condition
- CDK5RAP2 p.Arg1558Ter Pathogenic ★★ same condition
- CDK5RAP2 p.Arg427Ter Pathogenic ★★ same condition
- CDK5RAP2 p.Gln1743Ter Pathogenic ★★ same condition
- CDK5RAP2 p.Glu1516Ter Pathogenic ★★ same condition
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-glu1683 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown