CDK8 p.His235=
c.705C>T · rs17083996 · VCV3025053
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.34%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.76 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 5.9 | GERP 2.4, phastCons 1 |
| Overall | ||
| CADD | 13.03 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.34%
African / African-American · 1,001/74,844 alleles
Filtering AF
1.27%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.24%
Overall
0.0907%
1,462/1,611,970 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.34% | 75 |
| Middle Eastern | 0.363% | 275 |
| Ashkenazi Jewishnot grpmax-eligible | 0.203% | 493 |
| South Asian | 0.0967% | 1,035 |
| Remaining individualsnot grpmax-eligible | 0.0945% | 1,058 |
| Admixed American | 0.06% | 1,665 |
| European (non-Finnish) | 0.0165% | 6,044 |
| Finnishnot grpmax-eligible | 0.00157% | 63,858 |
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.His235=
- Coding
- c.705C>T
- MANE Select
- NM_001260
- dbSNP
- rs17083996
- Type
- single nucleotide variant
- Location
- chr13:26393425 (GRCh38)
- Gene constraint
- LOEUF 0.646 · pLI 0.47 (gnomAD)
- Structure
- AlphaFold pLDDT 80.75 · 36 PDB
- Residue 235
- 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-his235 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown