Is CCNK p.Pro110Ser (c.328C>T) pathogenic?

CCNK p.Pro110Ser (c.328C>T) is classified Uncertain significance in CCNK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-27). AlphaMissense: likely pathogenic (0.9998); Absent from gnomAD v4.1.

How common is CCNK p.Pro110Ser (c.328C>T) in the general population?

CCNK p.Pro110Ser (c.328C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCNK p.Pro110Ser (c.328C>T)?

AlphaMissense predicts likely pathogenic (score 0.9998) — an in-silico prediction, not a clinical call.

CCNK p.Pro110Ser

c.328C>T · VCV4222162

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9998 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9998	likely pathogenic · top 7% in CCNK
REVEL	0.524	indeterminate
SaProt	LLR -13.59	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 2,943 bp · p 7.9e-10 · regional, not allelic
Overall
CADD	28.5	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: CCNK
Protein: p.Pro110Ser
Coding: c.328C>T
MANE Select: NM_001099402
Type: single nucleotide variant
Location: chr14:99495546 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.43 · 43 PDB

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

Similar variants

CCNK p.Arg48Gln Uncertain significance ★★ ⚠ same type
CCNK p.Arg80Cys Uncertain significance ★★ ⚠ same type
CCNK p.Val246Ile Uncertain significance ★★ ⚠ same type
CCNK c.280-5T>C Benign ★★ same type
CCNK p.Ser11= Likely benign ★★ same type
CCNK p.Lys111Glu Likely pathogenic ★ same type
CCNK p.Ala54Thr Uncertain significance ★ ⚠ same type
CCNK p.Arg121Cys 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/ccnk-p-pro110ser (accessed [today's date]).

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