Is GBE1 p.Glu672= (c.2016G>A) pathogenic?

GBE1 p.Glu672= (c.2016G>A) is classified Benign/Likely benign in GBE1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-11). Rare (popmax 0.229%, sas); Associated with glycogen storage disease due to glycogen branching enzyme deficiency.

What condition is associated with GBE1 p.Glu672= (c.2016G>A)?

GBE1 p.Glu672= (c.2016G>A) is associated with glycogen storage disease due to glycogen branching enzyme deficiency (ClinVar).

How common is GBE1 p.Glu672= (c.2016G>A) in the general population?

GBE1 p.Glu672= (c.2016G>A) is rare (popmax 0.229%, sas) (gnomAD).

GBE1 p.Glu672=

Q: How is Glycogen storage disease due to glycogen branching enzyme deficiency inherited?

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

c.2016G>A · rs571448518 · VCV733064

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.229%, sas)

Conditions

glycogen storage disease due to glycogen branching enzyme deficiency

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	GERP -3
Overall
CADD	4.181	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.229% South Asian · 207/90,530 alleles

Filtering AF 0.203% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.193%

Overall 0.0132% 212/1,610,448 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.229%	437
Remaining individualsnot grpmax-eligible	0.00641%	15,596
European (non-Finnish)	8.49e-05%	1,177,734

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.Glu672=
Coding: c.2016G>A
MANE Select: NM_000158
dbSNP: rs571448518
Type: single nucleotide variant
Location: chr3:81499146 (GRCh38)
Gene constraint: LOEUF 1.211 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.30 · 3 PDB
Residue 672: a β-strand

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

Disease context

glycogen storage disease due to glycogen branching enzyme deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Glycogen storage disease due to glycogen branching enzyme deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

GBE1 p.Glu672Asp 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-glu672 (accessed [today's date]).

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