Is AGL p.Pro1345fs (c.4034delinsAT) pathogenic?

AGL p.Pro1345fs (c.4034delinsAT) is classified Likely pathogenic in AGL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-18). Associated with glycogen storage disease III.

What condition is associated with AGL p.Pro1345fs (c.4034delinsAT)?

AGL p.Pro1345fs (c.4034delinsAT) is associated with glycogen storage disease III (ClinVar).

AGL p.Pro1345fs

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.4034delinsAT · VCV4814453

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 30 of 34
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP 1, phastCons 1

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

Variant & gene context

Gene: AGL
Protein: p.Pro1345fs
Coding: c.4034delinsAT
MANE Select: NM_000642
Type: Indel
Location: chr1:99913611 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.88 · 1 PDB
Residue 1345: a β-strand; 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.His666_Gln667delinsTer Pathogenic/Likely pathogenic ★★ same condition
AGL p.Leu563fs Pathogenic/Likely pathogenic ★★ same condition
AGL c.2001+8_2001+9delinsCT Likely benign ★★ same condition
AGL c.1612-14_1632delinsCC Likely pathogenic ★ same condition
AGL c.401_460+75delinsTATTACAT Likely pathogenic ★ same condition
AGL c.4162-5_4162-1delinsCTAGTGAAT Likely pathogenic ★ same condition
AGL p.Lys1176fs Likely pathogenic ★ same condition
AGL p.Met1064fs 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-pro1345fs (accessed [today's date]).

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