Is CCNK p.His476fs (c.1426del) pathogenic?

CCNK p.His476fs (c.1426del) is classified Uncertain significance in CCNK (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-01-19). Very rare (popmax 0.0034%, amr); Associated with CCNK-related disorder.

What condition is associated with CCNK p.His476fs (c.1426del)?

CCNK p.His476fs (c.1426del) is associated with CCNK-related disorder (ClinVar).

How common is CCNK p.His476fs (c.1426del) in the general population?

CCNK p.His476fs (c.1426del) is very rare (popmax 0.0034%, amr) (gnomAD).

CCNK p.His476fs

c.1426del · rs1302182253 · VCV3033144

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0034%, amr)

Conditions

CCNK-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.4	GERP -0.84, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0034% Admixed American · 1/29,418 alleles

Overall 9.19e-05% 1/1,087,816 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.His476fs
Coding: c.1426del
MANE Select: NM_001144995 · reported on NM_001099402
dbSNP: rs1302182253
Type: Deletion
Location: chr14:99510461 (GRCh38)

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

Disease context

CCNK-related disorder

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-his476fs (accessed [today's date]).

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