Is AGL p.Pro548fs (c.1640_1641insGCTGG) pathogenic?

AGL p.Pro548fs (c.16401641insGCTGG) is classified Likely pathogenic in AGL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-17). Absent from gnomAD; Associated with glycogen storage disease III.

What condition is associated with AGL p.Pro548fs (c.1640_1641insGCTGG)?

AGL p.Pro548fs (c.1640_1641insGCTGG) is associated with glycogen storage disease III (ClinVar).

How common is AGL p.Pro548fs (c.1640_1641insGCTGG) in the general population?

AGL p.Pro548fs (c.1640_1641insGCTGG) is absent from gnomAD (gnomAD).

AGL p.Pro548fs

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.1640_1641insGCTGG · rs2524635966 · VCV1725389

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

glycogen storage disease III

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	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 11	GERP 1.6, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AGL
Protein: p.Pro548fs
Coding: c.1640_1641insGCTGG
MANE Select: NM_000642
dbSNP: rs2524635966
Type: Insertion
Location: chr1:99879951 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.88 · 1 PDB
Residue 548: the 'amylo-1,6-glucosidase' region

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.Pro548Arg Uncertain significance ★ ⚠ same residue
AGL p.Pro548= Likely benign ★ same residue
AGL p.Asn13fs Pathogenic/Likely pathogenic ★★ same condition
AGL c.965_966insTGACAGTTTTAATCTCTTTGTAGATATTTGCATTTAAGGTATCATCTTTTCTTTCTTTTAGAAAATAGTGACAGTTTTAATCTCTTTGAAGATCTCTGCATTTAAGGTATAATCTGTTCTTTCTTTTAGAAAATAGAAAATAG Likely pathogenic ★ same condition
AGL p.Asp1420fs Pathogenic ★ same condition
AGL p.His709fs Likely pathogenic ★ same condition
AGL p.Leu1452fs Likely pathogenic ★ same condition
AGL p.Lys206fs 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-pro548fs (accessed [today's date]).

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