Is CHKB p.Glu336del (c.1005AGA[1]) pathogenic?

CHKB p.Glu336del (c.1005AGA[1]) is classified Uncertain significance in CHKB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-21). Ultra-rare (popmax 0.012%, afr); Associated with megaconial type congenital muscular dystrophy.

What condition is associated with CHKB p.Glu336del (c.1005AGA[1])?

CHKB p.Glu336del (c.1005AGA[1]) is associated with megaconial type congenital muscular dystrophy (ClinVar).

How common is CHKB p.Glu336del (c.1005AGA[1]) in the general population?

CHKB p.Glu336del (c.1005AGA[1]) is ultra-rare (popmax 0.012%, afr) (gnomAD).

How is Megaconial congenital muscular dystrophy inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CHKB p.Glu336del

c.1005AGA[1] · rs778645316 · VCV2688775

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Conditions

megaconial type congenital muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.33	GERP -2.6, phastCons 0.57
Overall
CADD	18.21	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% African / African-American · 9/74,864 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00161% 26/1,613,804 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,318
Admixed American	0.005%	19,994
East Asian	0.00446%	22,442
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
South Asian	0.00329%	30,355
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	0.000593%	168,566

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.Glu336del
Coding: c.1005AGA[1]
MANE Select: NM_005198
dbSNP: rs778645316
Type: Microsatellite
Location: chr22:50579748 (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 336: a UniProt-annotated variant site (in mdcmc; loss of choline kinase activity; decreased amount of phosphatidylcholine in patients cells); a UniProt-annotated variant site (in mdcmc); an α-helix

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

Disease context

megaconial type congenital muscular dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Megaconial congenital muscular dystrophy (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

CHKB p.Glu336Lys Uncertain significance ★★ ⚠ same residue
CHKB p.Glu230fs Pathogenic ★ same condition
CHKB p.Gln51Ter Pathogenic/Likely pathogenic ★★ same condition
CHKB p.Phe189fs Pathogenic/Likely pathogenic ★★ same condition
CHKB c.*208T>G Uncertain significance ★★ same condition
CHKB p.Ala361Val Uncertain significance ★★ ⚠ same condition
CHKB p.Arg344Trp Uncertain significance ★★ ⚠ same condition
CHKB p.Arg62Cys 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-glu336del (accessed [today's date]).

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