Is CCNK p.Pro552Thr (c.1654C>A) pathogenic?

CCNK p.Pro552Thr (c.1654C>A) is classified Uncertain significance in CCNK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.1783); Very rare (popmax 0.00458%, nfe).

How common is CCNK p.Pro552Thr (c.1654C>A) in the general population?

CCNK p.Pro552Thr (c.1654C>A) is very rare (popmax 0.00458%, nfe) (gnomAD).

What do computational predictors say about CCNK p.Pro552Thr (c.1654C>A)?

AlphaMissense predicts likely benign (score 0.1783) — an in-silico prediction, not a clinical call.

CCNK p.Pro552Thr

c.1654C>A · rs753951143 · VCV2215076

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1783 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00458%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1783	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -9.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.7	GERP 1.3, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 171 bp · p 5.8e-05 · regional, not allelic
Overall
CADD	23.2	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 0.00458% European (non-Finnish) · 50/1,091,452 alleles

Filtering AF 0.00352% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00318%

Overall 0.0037% 53/1,431,018 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00458%	21,829
African / African-American	0.00298%	33,526
Remaining individualsnot grpmax-eligible	0.00183%	54,710

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.Pro552Thr
Coding: c.1654C>A
MANE Select: NM_001144995 · reported on NM_001099402
dbSNP: rs753951143
Type: single nucleotide variant
Location: chr14:99510693 (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-pro552thr (accessed [today's date]).

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