Is CCNK p.Pro557His (c.1670C>A) pathogenic?

CCNK p.Pro557His (c.1670C>A) is classified Uncertain significance in CCNK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-08). AlphaMissense: ambiguous (0.3943); Very rare (popmax 0.000186%, nfe).

How common is CCNK p.Pro557His (c.1670C>A) in the general population?

CCNK p.Pro557His (c.1670C>A) is very rare (popmax 0.000186%, nfe) (gnomAD).

What do computational predictors say about CCNK p.Pro557His (c.1670C>A)?

AlphaMissense predicts ambiguous (score 0.3943) — an in-silico prediction, not a clinical call.

CCNK p.Pro557His

c.1670C>A · rs2504059609 · VCV2324800

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3943 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000186%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3943	ambiguous
REVEL	0.385	indeterminate
SaProt	LLR -8.99	tolerated
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.2	GERP 0.087, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 171 bp · p 5.8e-05 · regional, not allelic
Overall
CADD	20.9	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 0.000186% European (non-Finnish) · 2/1,075,252 alleles

Filtering AF 3.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.2e-05%

Overall 0.000159% 2/1,255,080 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.Pro557His
Coding: c.1670C>A
MANE Select: NM_001144995 · reported on NM_001099402
dbSNP: rs2504059609
Type: single nucleotide variant
Location: chr14:99510709 (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-pro557his (accessed [today's date]).

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