Is CDK8 p.Asn245Asp (c.733A>G) pathogenic?

CDK8 p.Asn245Asp (c.733A>G) is classified Uncertain significance in CDK8 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-30). AlphaMissense: likely pathogenic (0.9628); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CDK8 p.Asn245Asp (c.733A>G)?

CDK8 p.Asn245Asp (c.733A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CDK8 p.Asn245Asp (c.733A>G) in the general population?

CDK8 p.Asn245Asp (c.733A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK8 p.Asn245Asp (c.733A>G)?

AlphaMissense predicts likely pathogenic (score 0.9628) — an in-silico prediction, not a clinical call.

CDK8 p.Asn245Asp

c.733A>G · rs2542441624 · VCV2247169

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9628 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9628	likely pathogenic
REVEL	0.244	benign-leaning
SaProt	LLR -10.59	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 16 kb · p 1.1e-18 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDK8
Protein: p.Asn245Asp
Coding: c.733A>G
MANE Select: NM_001260
dbSNP: rs2542441624
Type: single nucleotide variant
Location: chr13:26393453 (GRCh38)
Gene constraint: LOEUF 0.646 · pLI 0.47 (gnomAD)
Structure: AlphaFold pLDDT 80.75 · 36 PDB
Residue 245: the protein kinase domain

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.Asn383Asp Uncertain significance ★ ⚠ same condition
CDK8 p.Asp42His Uncertain significance ★ ⚠ same condition
CDK8 p.Gln440His Uncertain significance ★ ⚠ same condition
CDK8 p.Glu12Asp 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-asn245asp (accessed [today's date]).

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