Is CKB p.Ala158Pro (c.472G>C) pathogenic?

CKB p.Ala158Pro (c.472G>C) is classified Uncertain significance in CKB (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-01). AlphaMissense: likely pathogenic (0.986); Absent from gnomAD v4.1.

How common is CKB p.Ala158Pro (c.472G>C) in the general population?

CKB p.Ala158Pro (c.472G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CKB p.Ala158Pro (c.472G>C)?

AlphaMissense predicts likely pathogenic (score 0.986) — an in-silico prediction, not a clinical call.

CKB p.Ala158Pro

c.472G>C · VCV4868986

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.986 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.986	likely pathogenic
REVEL	0.202	benign-leaning
SaProt	LLR -13.93	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -4.6, phastCons 0.99
Regional constraint	o/e 0.77	unconstrained · MANE · 2,236 bp · p 2.4e-06 · regional, not allelic
Overall
CADD	25.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CKB
Protein: p.Ala158Pro
Coding: c.472G>C
MANE Select: NM_001823
Type: single nucleotide variant
Location: chr14:103521827 (GRCh38)
Gene constraint: LOEUF 0.724 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 95.59 · 6 PDB
Residue 158: the phosphagen kinase c-terminal domain; an α-helix

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

Similar variants

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
CKB p.Asp374Asn 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-ala158pro (accessed [today's date]).

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