Is CCNK p.Pro414Leu (c.1241C>T) pathogenic?

CCNK p.Pro414Leu (c.1241C>T) is classified Uncertain significance in CCNK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: ambiguous (0.3972); Ultra-rare (popmax 0.0137%, afr).

How common is CCNK p.Pro414Leu (c.1241C>T) in the general population?

CCNK p.Pro414Leu (c.1241C>T) is ultra-rare (popmax 0.0137%, afr) (gnomAD).

What do computational predictors say about CCNK p.Pro414Leu (c.1241C>T)?

AlphaMissense predicts ambiguous (score 0.3972) — an in-silico prediction, not a clinical call.

CCNK p.Pro414Leu

c.1241C>T · VCV4856890

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3972 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0137%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3972	ambiguous
REVEL	0.138	moderately benign-leaning
SaProt	LLR -9.02	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 5.3	GERP 1.2, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 7,692 bp · p 0.0051 · regional, not allelic
Overall
CADD	23.3	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 0.0137% African / African-American · 10/73,160 alleles

Filtering AF 0.00739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00562%

Overall 0.00115% 18/1,565,390 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0137%	7,316
Admixed American	0.0018%	55,432
South Asian	0.00115%	86,630
European (non-Finnish)	0.000518%	192,939

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.Pro414Leu
Coding: c.1241C>T
MANE Select: NM_001144995 · reported on NM_001099402
Type: single nucleotide variant
Location: chr14:99510280 (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-pro414leu (accessed [today's date]).

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