Is AGL p.Asp562Ter (c.1680_1683dup) pathogenic?

AGL p.Asp562Ter (c.16801683dup) is classified Likely pathogenic in AGL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-01). Very rare (popmax 0.00017%, nfe); Associated with glycogen storage disease III.

What condition is associated with AGL p.Asp562Ter (c.1680_1683dup)?

AGL p.Asp562Ter (c.1680_1683dup) is associated with glycogen storage disease III (ClinVar).

How common is AGL p.Asp562Ter (c.1680_1683dup) in the general population?

AGL p.Asp562Ter (c.1680_1683dup) is very rare (popmax 0.00017%, nfe) (gnomAD).

AGL p.Asp562Ter

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

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

c.1680_1683dup · rs2524636528 · VCV2674874

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

glycogen storage disease III

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 13 of 34
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP -0.22, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,818 alleles

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

Overall 0.000137% 2/1,461,476 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: AGL
Protein: p.Asp562Ter
Coding: c.1680_1683dup
MANE Select: NM_000642
dbSNP: rs2524636528
Type: Duplication
Location: chr1:99879990 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.88 · 1 PDB
Residue 562: the 'amylo-1,6-glucosidase' region; an α-helix

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

Disease context

glycogen storage disease III — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Inheritance: Autosomal recessive
Onset: Childhood, Infancy
Prevalence: 1-9 / 100 000 (United States)

Similar variants

AGL p.Asp562= Likely benign ★ same residue
AGL p.Arg1270Ter Pathogenic/Likely pathogenic ★★ same condition
AGL p.Arg898fs Pathogenic ★★ same condition
AGL p.Asn1304fs Pathogenic/Likely pathogenic ★★ same condition
AGL p.Asn84fs Pathogenic/Likely pathogenic ★★ same condition
AGL p.Gly1442fs Pathogenic ★★ same condition
AGL p.Ile336fs Pathogenic/Likely pathogenic ★★ same condition
AGL p.Ile847fs 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/agl-p-asp562ter (accessed [today's date]).

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