Is CDK14 p.Ser465Pro (c.1393T>C) pathogenic?

CDK14 p.Ser465Pro (c.1393T>C) is classified Uncertain significance in CDK14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely benign (0.0682); Ultra-rare (popmax 0.0651%, amr).

How common is CDK14 p.Ser465Pro (c.1393T>C) in the general population?

CDK14 p.Ser465Pro (c.1393T>C) is ultra-rare (popmax 0.0651%, amr) (gnomAD).

What do computational predictors say about CDK14 p.Ser465Pro (c.1393T>C)?

AlphaMissense predicts likely benign (score 0.0682) — an in-silico prediction, not a clinical call.

CDK14 p.Ser465Pro

c.1393T>C · VCV4651506

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0682 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0651%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0682	likely benign
REVEL	0.265	benign-leaning
SaProt	LLR -7.19	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.9	GERP 3.7, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 522 kb · p 0.00055 · regional, not allelic
Overall
CADD	23.5	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 0.0651% Admixed American · 39/59,926 alleles

Filtering AF 0.0488% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0433%

Overall 0.00242% 39/1,611,250 alleles · ultra-rare exomes 8/1,459,128 · genomes 31/152,122 · 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: CDK14
Protein: p.Ser465Pro
Coding: c.1393T>C
MANE Select: NM_001287135
Type: single nucleotide variant
Location: chr7:91118163 (GRCh38)
Gene constraint: LOEUF 0.894 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.10
Residue 465: the 'disordered' region

Full CDK14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDK14 p.Pro61= Benign ★★ same type
CDK14 c.124-16986G>A Uncertain significance ★ same type
CDK14 c.124-17003A>G Uncertain significance ★ same type
CDK14 c.124-17015A>T Uncertain significance ★ same type
CDK14 p.Ala382Val Uncertain significance ★ ⚠ same type
CDK14 p.Arg117Trp Uncertain significance ★ ⚠ same type
CDK14 p.Arg250His Uncertain significance ★ ⚠ same type
CDK14 p.Arg370Cys 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/cdk14-p-ser465pro (accessed [today's date]).

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