CDK8 p.Asp48=
c.144C>T · VCV4681390
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0366%, 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 3.9 | GERP -0.36, phastCons 1 |
| Overall | ||
| CADD | 11.49 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0366%
Middle Eastern · 2/5,458 alleles
Filtering AF
0.00641%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00264%
Overall
0.000345%
5/1,449,056 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0366% | 2,729 |
| Remaining individualsnot grpmax-eligible | 0.00364% | 27,443 |
| European (non-Finnish) | 9.14e-05% | 1,093,928 |
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.Asp48=
- Coding
- c.144C>T
- MANE Select
- NM_001260
- Type
- single nucleotide variant
- Location
- chr13:26337582 (GRCh38)
- Gene constraint
- LOEUF 0.646 · pLI 0.47 (gnomAD)
- Structure
- AlphaFold pLDDT 80.75 · 36 PDB
- Residue 48
- the protein kinase domain
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-asp48 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown