Is CCNK p.Ser259Ala (c.775T>G) pathogenic?

CCNK p.Ser259Ala (c.775T>G) is classified Uncertain significance in CCNK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-01). AlphaMissense: ambiguous (0.42); Very rare (popmax 8.48e-05%, nfe).

How common is CCNK p.Ser259Ala (c.775T>G) in the general population?

CCNK p.Ser259Ala (c.775T>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CCNK p.Ser259Ala (c.775T>G)?

AlphaMissense predicts ambiguous (score 0.42) — an in-silico prediction, not a clinical call.

CCNK p.Ser259Ala

c.775T>G · VCV3487462

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.42 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.42	ambiguous
REVEL	0.122	moderately benign-leaning
SaProt	LLR -4.65	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 1,995 bp · p 1.1e-11 · regional, not allelic
Overall
CADD	24.0	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 8.48e-05% European (non-Finnish) · 1/1,179,606 alleles

Overall 6.84e-05% 1/1,461,400 alleles · very rare

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.Ser259Ala
Coding: c.775T>G
MANE Select: NM_001144995 · reported on NM_001099402
Type: single nucleotide variant
Location: chr14:99502748 (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-ser259ala (accessed [today's date]).

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