Is CCNK p.Val12Ile (c.34G>A) pathogenic?

CCNK p.Val12Ile (c.34G>A) is classified Uncertain significance in CCNK (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-17). AlphaMissense: likely benign (0.0612); Very rare (popmax 8.48e-05%, nfe).

How common is CCNK p.Val12Ile (c.34G>A) in the general population?

CCNK p.Val12Ile (c.34G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CCNK p.Val12Ile (c.34G>A)?

AlphaMissense predicts likely benign (score 0.0612) — an in-silico prediction, not a clinical call.

CCNK p.Val12Ile

c.34G>A · rs1595307990 · VCV2268000

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0612 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0612	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -7.37	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 2,943 bp · p 7.9e-10 · regional, not allelic
Overall
CADD	19.93	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 8.48e-05% European (non-Finnish) · 1/1,178,884 alleles

Overall 6.86e-05% 1/1,457,808 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.Val12Ile
Coding: c.34G>A
MANE Select: NM_001099402
dbSNP: rs1595307990
Type: single nucleotide variant
Location: chr14:99492711 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.43 · 43 PDB

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

Similar variants

CCNK p.Arg48Gln Uncertain significance ★★ ⚠ same type
CCNK p.Arg80Cys Uncertain significance ★★ ⚠ same type
CCNK p.Val246Ile Uncertain significance ★★ ⚠ same type
CCNK c.280-5T>C Benign ★★ same type
CCNK p.Ser11= Likely benign ★★ same type
CCNK p.Lys111Glu Likely pathogenic ★ same type
CCNK p.Ala54Thr Uncertain significance ★ ⚠ same type
CCNK p.Arg121Cys Uncertain significance ★ ⚠ same type

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-val12ile (accessed [today's date]).

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