Is CDK10 p.Pro348Ser (c.1042C>T) pathogenic?

CDK10 p.Pro348Ser (c.1042C>T) is classified Uncertain significance in CDK10 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-04). AlphaMissense: likely benign (0.0723); Ultra-rare (popmax 0.0489%, amr); Associated with Inborn genetic diseases.

What condition is associated with CDK10 p.Pro348Ser (c.1042C>T)?

CDK10 p.Pro348Ser (c.1042C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDK10 p.Pro348Ser (c.1042C>T) in the general population?

CDK10 p.Pro348Ser (c.1042C>T) is ultra-rare (popmax 0.0489%, amr) (gnomAD).

What do computational predictors say about CDK10 p.Pro348Ser (c.1042C>T)?

AlphaMissense predicts likely benign (score 0.0723) — an in-silico prediction, not a clinical call.

CDK10 p.Pro348Ser

c.1042C>T · rs758922637 · VCV2309983

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0723 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0489%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0723	likely benign
REVEL	0.153	moderately benign-leaning
SaProt	LLR -4.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.77	GERP -0.082
Regional constraint	o/e 1.21	unconstrained · MANE · 8,978 bp · p 2.4e-06 · regional, not allelic
Overall
CADD	3.991	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0489% Admixed American · 29/59,316 alleles

Filtering AF 0.035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0302%

Overall 0.00187% 30/1,604,038 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0489%	2,045
Remaining individualsnot grpmax-eligible	0.00161%	62,098

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.Pro348Ser
Coding: c.1042C>T
MANE Select: NM_052988
dbSNP: rs758922637
Type: single nucleotide variant
Location: chr16:89695651 (GRCh38)
Gene constraint: LOEUF 1.344 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.27
Residue 348: the 'disordered' region

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.Pro348Gln Conflicting classifications of pathogenicity ★ ⚠ 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-pro348ser (accessed [today's date]).

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