Is CDK8 p.Arg237Gln (c.710G>A) pathogenic?

CDK8 p.Arg237Gln (c.710G>A) is classified Uncertain significance in CDK8 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-02-06). AlphaMissense: likely pathogenic (0.961); Absent from gnomAD v4.1; Associated with intellectual developmental disorder with hypotonia and behavioral abnormalities.

How common is CDK8 p.Arg237Gln (c.710G>A) in the general population?

CDK8 p.Arg237Gln (c.710G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK8 p.Arg237Gln (c.710G>A)?

AlphaMissense predicts likely pathogenic (score 0.961) — an in-silico prediction, not a clinical call.

CDK8 p.Arg237Gln

Q: What condition is associated with CDK8 p.Arg237Gln (c.710G>A)?

CDK8 p.Arg237Gln (c.710G>A) is associated with intellectual developmental disorder with hypotonia and behavioral abnormalities (ClinVar).

c.710G>A · VCV3906862

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.961 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

intellectual developmental disorder with hypotonia and behavioral abnormalities

Computational evidence

Protein change
AlphaMissense	0.961	likely pathogenic
REVEL	0.391	indeterminate
SaProt	LLR -8.34	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 16 kb · p 1.1e-18 · regional, not allelic
Overall
CADD	34.0	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.Arg237Gln
Coding: c.710G>A
MANE Select: NM_001260
Type: single nucleotide variant
Location: chr13:26393430 (GRCh38)
Gene constraint: LOEUF 0.646 · pLI 0.47 (gnomAD)
Structure: AlphaFold pLDDT 80.75 · 36 PDB
Residue 237: the protein kinase domain; an α-helix

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

Disease context

intellectual developmental disorder with hypotonia and behavioral abnormalities — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDK8 p.Ser62Leu Pathogenic ★★ same condition
CDK8 p.Asn433Lys Uncertain significance ★★ ⚠ same condition
CDK8 p.Pro388Gln Uncertain significance ★★ ⚠ same condition
CDK8 c.934-28G>A Benign ★★ same condition
CDK8 p.Ala188Gly Likely pathogenic ★ same condition
CDK8 p.Arg178Gln Pathogenic ★ same condition
CDK8 p.Asp173His Likely pathogenic ★ same condition
CDK8 p.Gly30Val Likely pathogenic ★ 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-arg237gln (accessed [today's date]).

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