Is CDK14 p.Ile338Phe (c.1012A>T) pathogenic?

CDK14 p.Ile338Phe (c.1012A>T) is classified Uncertain significance in CDK14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-28). AlphaMissense: ambiguous (0.5345); Ultra-rare (popmax 0.0104%, nfe).

How common is CDK14 p.Ile338Phe (c.1012A>T) in the general population?

CDK14 p.Ile338Phe (c.1012A>T) is ultra-rare (popmax 0.0104%, nfe) (gnomAD).

What do computational predictors say about CDK14 p.Ile338Phe (c.1012A>T)?

AlphaMissense predicts ambiguous (score 0.5345) — an in-silico prediction, not a clinical call.

CDK14 p.Ile338Phe

c.1012A>T · VCV4651502

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5345 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0104%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5345	ambiguous
REVEL	0.324	indeterminate
SaProt	LLR -9.88	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 4.3, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 522 kb · p 0.00055 · regional, not allelic
Overall
CADD	24.6	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 0.0104% European (non-Finnish) · 122/1,178,472 alleles

Filtering AF 0.00885% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00829%

Overall 0.00769% 124/1,612,306 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0104%	9,660
Admixed American	0.00167%	60,000
Remaining individualsnot grpmax-eligible	0.0016%	62,426

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.Ile338Phe
Coding: c.1012A>T
MANE Select: NM_001287135
Type: single nucleotide variant
Location: chr7:90984212 (GRCh38)
Gene constraint: LOEUF 0.894 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.10
Residue 338: the protein kinase domain

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-ile338phe (accessed [today's date]).

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