Is CCNK p.Leu165= (c.495A>T) pathogenic?

CCNK p.Leu165= (c.495A>T) is classified Benign in CCNK (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-30). Low-frequency (popmax 3.88%, eas); Associated with CCNK-related disorder.

What condition is associated with CCNK p.Leu165= (c.495A>T)?

CCNK p.Leu165= (c.495A>T) is associated with CCNK-related disorder (ClinVar).

How common is CCNK p.Leu165= (c.495A>T) in the general population?

CCNK p.Leu165= (c.495A>T) is low-frequency (popmax 3.88%, eas) (gnomAD).

CCNK p.Leu165=

c.495A>T · rs2069493 · VCV3039124

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 3.88%, eas)

Conditions

CCNK-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.9	GERP -1.8, phastCons 1
Overall
CADD	10.32	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.88% East Asian · 1,639/42,244 alleles

Filtering AF 3.72% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.66%

Overall 0.28% 4,329/1,548,782 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	3.88%	26
Admixed American	3.71%	27
Finnishnot grpmax-eligible	0.439%	228
Ashkenazi Jewishnot grpmax-eligible	0.435%	230
Remaining individualsnot grpmax-eligible	0.228%	439
Middle Eastern	0.0502%	1,992
African / African-American	0.0423%	2,366
South Asian	0.0328%	3,047
European (non-Finnish)	0.0208%	4,808

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.Leu165=
Coding: c.495A>T
MANE Select: NM_001144995 · reported on NM_001099402
dbSNP: rs2069493
Type: single nucleotide variant
Location: chr14:99500849 (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-leu165 (accessed [today's date]).

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