Is CKB p.Lys45Arg (c.134A>G) pathogenic?

CKB p.Lys45Arg (c.134A>G) is classified Uncertain significance in CKB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.0701); Very rare (popmax 0.00334%, amr).

How common is CKB p.Lys45Arg (c.134A>G) in the general population?

CKB p.Lys45Arg (c.134A>G) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about CKB p.Lys45Arg (c.134A>G)?

AlphaMissense predicts likely benign (score 0.0701) — an in-silico prediction, not a clinical call.

CKB p.Lys45Arg

c.134A>G · VCV4229274

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0701 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0701	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -8.72	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 1	GERP 0.57, phastCons 0.99
Regional constraint	o/e 1.05	unconstrained · MANE · 151 bp · p 0.68 · regional, not allelic
Overall
CADD	20.6	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 0.00334% Admixed American · 2/59,918 alleles

Filtering AF 0.000554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000186% 3/1,611,310 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,959
African / African-American	0.00134%	74,664

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: CKB
Protein: p.Lys45Arg
Coding: c.134A>G
MANE Select: NM_001823
Type: single nucleotide variant
Location: chr14:103522360 (GRCh38)
Gene constraint: LOEUF 0.724 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 95.59 · 6 PDB
Residue 45: the phosphagen kinase n-terminal domain; a cross-link site

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

Similar variants

CKB p.Ala158Pro Uncertain significance ★ ⚠ same type
CKB p.Ala175Pro Uncertain significance ★ ⚠ same type
CKB p.Arg252Cys Uncertain significance ★ ⚠ same type
CKB p.Asn124Ser Uncertain significance ★ ⚠ same type
CKB p.Asp113Gly Uncertain significance ★ ⚠ same type
CKB p.Asp119Asn Uncertain significance ★ ⚠ same type
CKB p.Asp18Asn Uncertain significance ★ ⚠ same type
CKB p.Asp190Asn 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/ckb-p-lys45arg (accessed [today's date]).

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