Is CHKB p.Glu100Asp (c.300G>C) pathogenic?

CHKB p.Glu100Asp (c.300G>C) is classified Uncertain significance in CHKB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). AlphaMissense: likely benign (0.2508); Very rare (popmax 0.000256%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CHKB p.Glu100Asp (c.300G>C)?

CHKB p.Glu100Asp (c.300G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CHKB p.Glu100Asp (c.300G>C) in the general population?

CHKB p.Glu100Asp (c.300G>C) is very rare (popmax 0.000256%, nfe) (gnomAD).

What do computational predictors say about CHKB p.Glu100Asp (c.300G>C)?

AlphaMissense predicts likely benign (score 0.2508) — an in-silico prediction, not a clinical call.

CHKB p.Glu100Asp

c.300G>C · VCV4614969

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2508 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000256%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2508	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -10.87	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.27	GERP -3, phastCons 0.99
Regional constraint	o/e 1.03	unconstrained · MANE · 3,597 bp · p 0.53 · regional, not allelic
Overall
CADD	21.3	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 0.000256% European (non-Finnish) · 3/1,172,770 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000208% 3/1,442,086 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: CHKB
Protein: p.Glu100Asp
Coding: c.300G>C
MANE Select: NM_005198
Type: single nucleotide variant
Location: chr22:50582282 (GRCh38)
Gene constraint: LOEUF 1.015 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 3 PDB
Residue 100: a UniProt-annotated variant site (in mdcmc; loss of choline kinase activity; decreased amount of phosphatidylcholine in patients cells); a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHKB p.Gln309Glu Uncertain significance ★★ ⚠ same condition
CHKB p.Glu97Asp Uncertain significance ★★ ⚠ same condition
CHKB p.Gly12Glu Uncertain significance ★★ ⚠ same condition
CHKB p.Gly190Glu Uncertain significance ★★ ⚠ same condition
CHKB p.Gly386Glu Uncertain significance ★★ ⚠ same condition
CHKB p.His315Arg Uncertain significance ★★ ⚠ same condition
CHKB p.Leu334Pro Uncertain significance ★★ ⚠ same condition
CHKB p.Leu371Met Uncertain significance ★★ ⚠ same condition

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/chkb-p-glu100asp (accessed [today's date]).

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