Is CDK10 p.Pro258Ser (c.772C>T) pathogenic?

CDK10 p.Pro258Ser (c.772C>T) is classified Uncertain significance in CDK10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-03). AlphaMissense: likely pathogenic (0.976); Very rare (popmax 0.000346%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CDK10 p.Pro258Ser (c.772C>T)?

CDK10 p.Pro258Ser (c.772C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDK10 p.Pro258Ser (c.772C>T) in the general population?

CDK10 p.Pro258Ser (c.772C>T) is very rare (popmax 0.000346%, nfe) (gnomAD).

What do computational predictors say about CDK10 p.Pro258Ser (c.772C>T)?

AlphaMissense predicts likely pathogenic (score 0.976) — an in-silico prediction, not a clinical call.

CDK10 p.Pro258Ser

c.772C>T · VCV3489147

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.976 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000346%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.976	likely pathogenic
REVEL	0.587	indeterminate
SaProt	LLR -13.50	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 0.41, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 8,978 bp · p 2.4e-06 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000346% European (non-Finnish) · 4/1,156,206 alleles

Filtering AF 8.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.000256% 4/1,564,668 alleles · very rare exomes 3/1,412,486 · genomes 1/152,182 · joint denominator

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: CDK10
Protein: p.Pro258Ser
Coding: c.772C>T
MANE Select: NM_052988
Type: single nucleotide variant
Location: chr16:89694768 (GRCh38)
Gene constraint: LOEUF 1.344 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.27
Residue 258: the protein kinase domain

Full CDK10 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

CDK10 p.Pro258Ala Uncertain significance ★ ⚠ same residue
CDK10 p.Arg345Gln Uncertain significance ★★ ⚠ same condition
CDK10 p.Arg57Gln Uncertain significance ★★ ⚠ same condition
CDK10 p.Arg57Trp Uncertain significance ★★ same condition
CDK10 p.Glu9Gln Uncertain significance ★★ ⚠ same condition
CDK10 p.Leu229Val Uncertain significance ★★ ⚠ same condition
CDK10 p.Leu269Val Uncertain significance ★★ same condition
CDK10 p.Met195Val 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/cdk10-p-pro258ser (accessed [today's date]).

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