Is CDK8 p.Val193Gly (c.578T>G) pathogenic?

CDK8 p.Val193Gly (c.578T>G) is classified Pathogenic in CDK8 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-09-11). AlphaMissense: likely pathogenic (0.9982); Absent from gnomAD v4.1; Associated with intellectual developmental disorder with hypotonia and behavioral abnormalities.

How common is CDK8 p.Val193Gly (c.578T>G) in the general population?

CDK8 p.Val193Gly (c.578T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK8 p.Val193Gly (c.578T>G)?

AlphaMissense predicts likely pathogenic (score 0.9982) — an in-silico prediction, not a clinical call.

CDK8 p.Val193Gly

Q: What condition is associated with CDK8 p.Val193Gly (c.578T>G)?

CDK8 p.Val193Gly (c.578T>G) is associated with intellectual developmental disorder with hypotonia and behavioral abnormalities (ClinVar).

c.578T>G · rs1875421510 · VCV805984

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9982 · 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	0.9982	likely pathogenic ✓ concordant with ClinVar
REVEL	0.684	pathogenic-leaning
SaProt	LLR -13.09	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.00	constrained · MANE · 46 bp · p 1.6e-05 · regional, not allelic
Overall
CADD	32.0	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.Val193Gly
Coding: c.578T>G
MANE Select: NM_001260
dbSNP: rs1875421510
Type: single nucleotide variant
Location: chr13:26385274 (GRCh38)
Gene constraint: LOEUF 0.646 · pLI 0.47 (gnomAD)
Structure: AlphaFold pLDDT 80.75 · 36 PDB
Residue 193: the protein kinase domain; a UniProt-annotated variant site (in iddhba; decreased protein kinase activity)

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-val193gly (accessed [today's date]).

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