Is GBE1 p.Asp668= (c.2004C>T) pathogenic?

GBE1 p.Asp668= (c.2004C>T) is classified Likely benign in GBE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-10). Very rare (popmax 0.00133%, afr); Associated with Glycogen storage disease IV, classic hepatic.

What condition is associated with GBE1 p.Asp668= (c.2004C>T)?

GBE1 p.Asp668= (c.2004C>T) is associated with Glycogen storage disease IV, classic hepatic, glycogen storage disease due to glycogen branching enzyme deficiency (ClinVar).

How common is GBE1 p.Asp668= (c.2004C>T) in the general population?

GBE1 p.Asp668= (c.2004C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

GBE1 p.Asp668=

c.2004C>T · rs757815784 · VCV1112260

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Glycogen storage disease IV, classic hepatic

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -4.7
Overall
CADD	0.282	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,984 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000434% 7/1,612,004 alleles · very rare exomes 7/1,459,718 · genomes 0/152,286 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,424
Finnishnot grpmax-eligible	0.00156%	63,936
African / African-Americangrpmax	0.00133%	74,984
European (non-Finnish)	0.000339%	294,723

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: GBE1
Protein: p.Asp668=
Coding: c.2004C>T
MANE Select: NM_000158
dbSNP: rs757815784
Type: single nucleotide variant
Location: chr3:81499158 (GRCh38)
Gene constraint: LOEUF 1.211 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.30 · 3 PDB

Full GBE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Glycogen storage disease IV, classic hepatic — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: glycogen storage disease due to glycogen branching enzyme deficiency

Similar variants

GBE1 p.Asp668Glu Uncertain significance ★ ⚠ same residue
GBE1 c.1109-1G>T Likely pathogenic ★★ same condition
GBE1 c.1236+1G>A Likely pathogenic ★★ same condition
GBE1 c.1336-1G>A Pathogenic/Likely pathogenic ★★ same condition
GBE1 c.143+1G>A Pathogenic ★★ same condition
GBE1 c.143+2T>C Pathogenic/Likely pathogenic ★★ same condition
GBE1 c.144-1G>C Pathogenic/Likely pathogenic ★★ same condition
GBE1 c.1618+1G>A Pathogenic/Likely pathogenic ★★ 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/gbe1-p-asp668 (accessed [today's date]).

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