Is CKB p.Asp190Asn (c.568G>A) pathogenic?

CKB p.Asp190Asn (c.568G>A) is classified Uncertain significance in CKB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely pathogenic (0.5739); Ultra-rare (popmax 0.02%, amr).

How common is CKB p.Asp190Asn (c.568G>A) in the general population?

CKB p.Asp190Asn (c.568G>A) is ultra-rare (popmax 0.02%, amr) (gnomAD).

What do computational predictors say about CKB p.Asp190Asn (c.568G>A)?

AlphaMissense predicts likely pathogenic (score 0.5739) — an in-silico prediction, not a clinical call.

CKB p.Asp190Asn

c.568G>A · rs754012287 · VCV2403693

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5739 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5739	likely pathogenic
REVEL	0.367	indeterminate
SaProt	LLR -12.62	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 0.84, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 2,236 bp · p 2.4e-06 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.02% Admixed American · 12/59,922 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00899%

Overall 0.000892% 13/1,457,528 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.02%	4,994
Remaining individualsnot grpmax-eligible	0.0016%	62,390

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.Asp190Asn
Coding: c.568G>A
MANE Select: NM_001823
dbSNP: rs754012287
Type: single nucleotide variant
Location: chr14:103521348 (GRCh38)
Gene constraint: LOEUF 0.724 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 95.59 · 6 PDB
Residue 190: the phosphagen kinase c-terminal domain

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.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-asp190asn (accessed [today's date]).

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