Is CDK10 p.Pro4Ala (c.10C>G) pathogenic?

CDK10 p.Pro4Ala (c.10C>G) is classified Likely benign in CDK10 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-01). AlphaMissense: likely benign (0.0546); Rare (popmax 0.613%, nfe).

How common is CDK10 p.Pro4Ala (c.10C>G) in the general population?

CDK10 p.Pro4Ala (c.10C>G) is rare (popmax 0.613%, nfe) (gnomAD).

What do computational predictors say about CDK10 p.Pro4Ala (c.10C>G)?

AlphaMissense predicts likely benign (score 0.0546) — an in-silico prediction, not a clinical call.

CDK10 p.Pro4Ala

c.10C>G · rs187319559 · VCV2570957

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0546 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.613%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0546	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -5.35	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 -0.14	GERP -0.15
Regional constraint	o/e 1.21	unconstrained · MANE · 8,978 bp · p 2.4e-06 · regional, not allelic
Overall
CADD	6.527	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

Grpmax group 0.613% European (non-Finnish) · 7,209/1,175,440 alleles

Filtering AF 0.601% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.597%

Overall 0.533% 8,552/1,603,842 alleles · rare exomes 7,894/1,451,764 · genomes 658/152,078 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.613%	163
Ashkenazi Jewishnot grpmax-eligible	0.565%	177
Finnishnot grpmax-eligible	0.562%	178
Remaining individualsnot grpmax-eligible	0.534%	187
Middle Eastern	0.436%	229
Admixed American	0.362%	276
South Asian	0.227%	441
African / African-American	0.0683%	1,465

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.Pro4Ala
Coding: c.10C>G
MANE Select: NM_052988
dbSNP: rs187319559
Type: single nucleotide variant
Location: chr16:89686720 (GRCh38)
Gene constraint: LOEUF 1.344 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.27

Full CDK10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDK10 p.Pro4= Likely benign ★ same residue
CDK10 c.608+1G>A Pathogenic ★★ same type
CDK10 c.609-1G>A Pathogenic/Likely pathogenic ★★ same type
CDK10 c.87+5G>A Pathogenic/Likely pathogenic ★★ same type
CDK10 p.Cys8Ter Pathogenic/Likely pathogenic ★★ same type
CDK10 p.Arg205Gln Uncertain significance ★★ ⚠ same type
CDK10 p.Arg345Gln Uncertain significance ★★ ⚠ same type
CDK10 p.Arg57Gln Uncertain significance ★★ ⚠ same type

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-pro4ala (accessed [today's date]).

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