Is CDK8 p.Ala68= (c.204A>G) pathogenic?

CDK8 p.Ala68= (c.204A>G) is classified Likely benign in CDK8 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-30). Ultra-rare (popmax 0.0177%, afr); Associated with Inborn genetic diseases.

What condition is associated with CDK8 p.Ala68= (c.204A>G)?

CDK8 p.Ala68= (c.204A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CDK8 p.Ala68= (c.204A>G) in the general population?

CDK8 p.Ala68= (c.204A>G) is ultra-rare (popmax 0.0177%, afr) (gnomAD).

CDK8 p.Ala68=

c.204A>G · rs371097459 · VCV2356496

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0177%, afr)

Conditions

Inborn genetic diseases

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	GERP -0.76, phastCons 1
Overall
CADD	12.62	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0177% African / African-American · 12/67,860 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00791%

Overall 0.000929% 13/1,399,582 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0177%	5,655
European (non-Finnish)	9.44e-05%	1,058,829

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.Ala68=
Coding: c.204A>G
MANE Select: NM_001260
dbSNP: rs371097459
Type: single nucleotide variant
Location: chr13:26337642 (GRCh38)
Gene constraint: LOEUF 0.646 · pLI 0.47 (gnomAD)
Structure: AlphaFold pLDDT 80.75 · 36 PDB
Residue 68: the protein kinase domain; an α-helix

Full CDK8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDK8 p.Met445Ile Uncertain significance ★★ ⚠ same condition
CDK8 p.Ala144Thr Uncertain significance ★ ⚠ same condition
CDK8 p.Arg356Gln Uncertain significance ★ ⚠ same condition
CDK8 p.Arg463Gln Uncertain significance ★ ⚠ same condition
CDK8 p.Asn245Asp Uncertain significance ★ ⚠ same condition
CDK8 p.Asn383Asp Uncertain significance ★ ⚠ same condition
CDK8 p.Asp42His Uncertain significance ★ ⚠ same condition
CDK8 p.Gln440His Uncertain significance ★ ⚠ 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/cdk8-p-ala68 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown