Is CDK14 p.Asp340His (c.1018G>C) pathogenic?

CDK14 p.Asp340His (c.1018G>C) is classified Uncertain significance in CDK14 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-15). AlphaMissense: likely pathogenic (0.9917); Absent from gnomAD v4.1.

How common is CDK14 p.Asp340His (c.1018G>C) in the general population?

CDK14 p.Asp340His (c.1018G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK14 p.Asp340His (c.1018G>C)?

AlphaMissense predicts likely pathogenic (score 0.9917) — an in-silico prediction, not a clinical call.

CDK14 p.Asp340His

c.1018G>C · VCV3265432

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9917 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9917	likely pathogenic
REVEL	0.817	moderately pathogenic-leaning
SaProt	LLR -10.86	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 4.3, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 522 kb · p 0.00055 · regional, not allelic
Overall
CADD	32.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDK14
Protein: p.Asp340His
Coding: c.1018G>C
MANE Select: NM_001287135
Type: single nucleotide variant
Location: chr7:90984218 (GRCh38)
Gene constraint: LOEUF 0.894 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.10
Residue 340: 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-asp340his (accessed [today's date]).

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