Is CDK14 p.Arg370Ser (c.1108C>A) pathogenic?

CDK14 p.Arg370Ser (c.1108C>A) is classified Uncertain significance in CDK14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: ambiguous (0.4503); Ultra-rare (popmax 0.014%, amr).

How common is CDK14 p.Arg370Ser (c.1108C>A) in the general population?

CDK14 p.Arg370Ser (c.1108C>A) is ultra-rare (popmax 0.014%, amr) (gnomAD).

What do computational predictors say about CDK14 p.Arg370Ser (c.1108C>A)?

AlphaMissense predicts ambiguous (score 0.4503) — an in-silico prediction, not a clinical call.

CDK14 p.Arg370Ser

c.1108C>A · rs748125989 · VCV2361390

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4503 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.014%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4503	ambiguous
REVEL	0.281	benign-leaning
SaProt	LLR -4.75	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.66 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.8	GERP 2.5, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 522 kb · p 0.00055 · regional, not allelic
Overall
CADD	26.2	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 0.014% Admixed American · 8/57,026 alleles

Filtering AF 0.00691% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00504%

Overall 0.00063% 9/1,428,344 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.014%	7,128
Remaining individualsnot grpmax-eligible	0.00163%	61,326

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.Arg370Ser
Coding: c.1108C>A
MANE Select: NM_001287135
dbSNP: rs748125989
Type: single nucleotide variant
Location: chr7:91079434 (GRCh38)
Gene constraint: LOEUF 0.894 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.10
Residue 370: the protein kinase domain

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

Similar variants

CDK14 p.Arg370Cys Uncertain significance ★ ⚠ same residue
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

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-arg370ser (accessed [today's date]).

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