Is GBE1 p.Ile614= (c.1842T>C) pathogenic?

GBE1 p.Ile614= (c.1842T>C) is classified Likely benign in GBE1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-31). Very rare (popmax 0.00223%, eas); Associated with Glycogen storage disease IV, classic hepatic.

What condition is associated with GBE1 p.Ile614= (c.1842T>C)?

GBE1 p.Ile614= (c.1842T>C) is associated with Glycogen storage disease IV, classic hepatic, glycogen storage disease due to glycogen branching enzyme deficiency (ClinVar).

How common is GBE1 p.Ile614= (c.1842T>C) in the general population?

GBE1 p.Ile614= (c.1842T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

GBE1 p.Ile614=

c.1842T>C · rs774354874 · VCV255387

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 -0.39	GERP -4.8
Overall
CADD	0.575	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,792 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,611,248 alleles · very rare exomes 3/1,459,196 · genomes 1/152,052 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,792
Remaining individualsnot grpmax-eligible	0.0016%	62,342
European (non-Finnish)	0.00017%	589,306

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.Ile614=
Coding: c.1842T>C
MANE Select: NM_000158
dbSNP: rs774354874
Type: single nucleotide variant
Location: chr3:81535287 (GRCh38)
Gene constraint: LOEUF 1.211 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.30 · 3 PDB
Residue 614: a β-strand

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 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
GBE1 c.1803+2T>C 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-ile614 (accessed [today's date]).

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