Is CCNK p.Pro531= (c.1593C>T) pathogenic?

CCNK p.Pro531= (c.1593C>T) is classified Likely benign in CCNK (ClinVar, Single submitter, 2 submitters; last evaluated 2024-07-15). Low-frequency (popmax 1.15%, afr).

How common is CCNK p.Pro531= (c.1593C>T) in the general population?

CCNK p.Pro531= (c.1593C>T) is low-frequency (popmax 1.15%, afr) (gnomAD).

CCNK p.Pro531=

c.1593C>T · rs376250447 · VCV3053554

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.15%, afr)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.193	benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -2.4	GERP -0.97
Overall
CADD	1.289	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.15% African / African-American · 667/57,924 alleles

Filtering AF 1.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.05%

Overall 0.0528% 744/1,409,416 alleles · low-frequency exomes 438/1,288,038 · genomes 306/121,378 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.15%	87
Remaining individualsnot grpmax-eligible	0.0806%	1,241
Admixed American	0.0509%	1,966
European (non-Finnish)	0.00157%	63,730

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.Pro531=
Coding: c.1593C>T
MANE Select: NM_001099402
dbSNP: rs376250447
Type: single nucleotide variant
Location: chr14:99510632 (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-pro531 (accessed [today's date]).

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