CDK8 p.Ala63=
c.189A>G · VCV4821994
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.128%, sas)
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 2.1 | GERP -1.9, phastCons 1 |
| Overall | ||
| CADD | 9.721 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.128%
South Asian · 74/57,664 alleles
Filtering AF
0.105%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0962%
Overall
0.00577%
83/1,438,986 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.128% | 779 |
| Remaining individualsnot grpmax-eligible | 0.0147% | 6,786 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0041% | 24,372 |
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
- CDK8
- Protein
- p.Ala63=
- Coding
- c.189A>G
- MANE Select
- NM_001260
- Type
- single nucleotide variant
- Location
- chr13:26337627 (GRCh38)
- Gene constraint
- LOEUF 0.646 · pLI 0.47 (gnomAD)
- Structure
- AlphaFold pLDDT 80.75 · 36 PDB
- Residue 63
- the protein kinase domain; an α-helix
Similar variants
- CDK8 p.Ser62Leu Pathogenic ★★ same type
- CDK8 p.Asn433Lys Uncertain significance ★★ ⚠ same type
- CDK8 p.Met445Ile Uncertain significance ★★ ⚠ same type
- CDK8 p.Pro388Gln Uncertain significance ★★ ⚠ same type
- CDK8 c.934-28G>A Benign ★★ same type
- CDK8 p.Ala188Gly Likely pathogenic ★ same type
- CDK8 p.Arg178Gln Pathogenic ★ same type
- CDK8 p.Asn156Ser 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/cdk8-p-ala63 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown