Is CCNK p.Arg374Trp (c.1120C>T) pathogenic?

CCNK p.Arg374Trp (c.1120C>T) is classified Uncertain significance in CCNK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-06). AlphaMissense: likely benign (0.2704); Very rare (popmax 0.00502%, nfe).

How common is CCNK p.Arg374Trp (c.1120C>T) in the general population?

CCNK p.Arg374Trp (c.1120C>T) is very rare (popmax 0.00502%, nfe) (gnomAD).

What do computational predictors say about CCNK p.Arg374Trp (c.1120C>T)?

AlphaMissense predicts likely benign (score 0.2704) — an in-silico prediction, not a clinical call.

CCNK p.Arg374Trp

c.1120C>T · VCV3997672

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2704 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00502%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2704	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -9.13	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.5	GERP 1.2, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 7,692 bp · p 0.0051 · regional, not allelic
Overall
CADD	24.3	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 0.00502% European (non-Finnish) · 59/1,174,606 alleles

Filtering AF 0.00396% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00362%

Overall 0.00389% 62/1,595,192 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00502%	19,909
African / African-American	0.00268%	37,306
Remaining individualsnot grpmax-eligible	0.00162%	61,762

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: CCNK
Protein: p.Arg374Trp
Coding: c.1120C>T
MANE Select: NM_001144995 · reported on NM_001099402
Type: single nucleotide variant
Location: chr14:99510159 (GRCh38)

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

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/ccnk-p-arg374trp (accessed [today's date]).

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