Is CDK8 p.Ser62Trp (c.185C>G) pathogenic?

CDK8 p.Ser62Trp (c.185C>G) is classified Likely pathogenic in CDK8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-11). AlphaMissense: likely pathogenic (0.9992); Absent from gnomAD v4.1; Associated with intellectual developmental disorder with hypotonia and behavioral abnormalities.

How common is CDK8 p.Ser62Trp (c.185C>G) in the general population?

CDK8 p.Ser62Trp (c.185C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK8 p.Ser62Trp (c.185C>G)?

AlphaMissense predicts likely pathogenic (score 0.9992) — an in-silico prediction, not a clinical call.

CDK8 p.Ser62Trp

Q: What condition is associated with CDK8 p.Ser62Trp (c.185C>G)?

CDK8 p.Ser62Trp (c.185C>G) is associated with intellectual developmental disorder with hypotonia and behavioral abnormalities (ClinVar).

c.185C>G · rs1565977796 · VCV3236205

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9992 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual developmental disorder with hypotonia and behavioral abnormalities

Computational evidence

Protein change
AlphaMissense	0.9992	likely pathogenic ✓ concordant with ClinVar
REVEL	0.686	pathogenic-leaning
SaProt	LLR -15.75	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 130 kb · p 6.4e-10 · 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.Ser62Trp
Coding: c.185C>G
MANE Select: NM_001260
dbSNP: rs1565977796
Type: single nucleotide variant
Location: chr13:26337623 (GRCh38)
Gene constraint: LOEUF 0.646 · pLI 0.47 (gnomAD)
Structure: AlphaFold pLDDT 80.75 · 36 PDB
Residue 62: the protein kinase domain; a UniProt-annotated variant site (in iddhba; decreased protein kinase activity); 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 residue
CDK8 p.Ser62Ter Pathogenic ★ same residue
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

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-ser62trp (accessed [today's date]).

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