Is CCNK p.Pro286Leu (c.857C>T) pathogenic?

CCNK p.Pro286Leu (c.857C>T) is classified Uncertain significance in CCNK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-07). AlphaMissense: likely benign (0.1172); Ultra-rare (popmax 0.0176%, sas).

How common is CCNK p.Pro286Leu (c.857C>T) in the general population?

CCNK p.Pro286Leu (c.857C>T) is ultra-rare (popmax 0.0176%, sas) (gnomAD).

What do computational predictors say about CCNK p.Pro286Leu (c.857C>T)?

AlphaMissense predicts likely benign (score 0.1172) — an in-silico prediction, not a clinical call.

CCNK p.Pro286Leu

c.857C>T · rs200034824 · VCV2213927

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1172 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1172	likely benign
REVEL	0.158	moderately benign-leaning
SaProt	LLR -8.73	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 7,692 bp · p 0.0051 · regional, not allelic
Overall
CADD	25.6	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 0.0176% South Asian · 16/91,042 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00912%

Overall 0.0101% 163/1,613,686 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0176%	5,690
European (non-Finnish)	0.0114%	8,804
East Asian	0.00892%	11,216
African / African-American	0.00533%	18,746
Admixed American	0.005%	19,999
Remaining individualsnot grpmax-eligible	0.0032%	31,239

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.Pro286Leu
Coding: c.857C>T
MANE Select: NM_001144995 · reported on NM_001099402
dbSNP: rs200034824
Type: single nucleotide variant
Location: chr14:99502830 (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-pro286leu (accessed [today's date]).

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