Is CCNK p.Arg419Gln (c.1256G>A) pathogenic?

CCNK p.Arg419Gln (c.1256G>A) is classified Uncertain significance in CCNK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). AlphaMissense: ambiguous (0.3839); Rare (popmax 0.121%, eas).

How common is CCNK p.Arg419Gln (c.1256G>A) in the general population?

CCNK p.Arg419Gln (c.1256G>A) is rare (popmax 0.121%, eas) (gnomAD).

What do computational predictors say about CCNK p.Arg419Gln (c.1256G>A)?

AlphaMissense predicts ambiguous (score 0.3839) — an in-silico prediction, not a clinical call.

CCNK p.Arg419Gln

c.1256G>A · rs779295552 · VCV2600992

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3839 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.121%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3839	ambiguous
REVEL	0.096	moderately benign-leaning
SaProt	LLR -3.52	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 6.6	GERP 1.2, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 7,692 bp · p 0.0051 · regional, not allelic
Overall
CADD	23.1	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 0.121% East Asian · 19/15,682 alleles

Filtering AF 0.0793% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0659%

Overall 0.00522% 40/766,052 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.121%	825
African / African-American	0.0175%	5,705
South Asian	0.00776%	12,887
Remaining individualsnot grpmax-eligible	0.00698%	14,332
European (non-Finnish)	0.00176%	56,829

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.Arg419Gln
Coding: c.1256G>A
MANE Select: NM_001144995 · reported on NM_001099402
dbSNP: rs779295552
Type: single nucleotide variant
Location: chr14:99510295 (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-arg419gln (accessed [today's date]).

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