Is AGL p.Ile9fs (c.24_25del) pathogenic?

AGL p.Ile9fs (c.2425del) is classified Pathogenic in AGL (ClinVar, Single submitter, 1 submitter; last evaluated 2020-06-09). Very rare (popmax 0.00017%, nfe); Associated with glycogen storage disease III.

What condition is associated with AGL p.Ile9fs (c.24_25del)?

AGL p.Ile9fs (c.24_25del) is associated with glycogen storage disease III (ClinVar).

How common is AGL p.Ile9fs (c.24_25del) in the general population?

AGL p.Ile9fs (c.24_25del) is very rare (popmax 0.00017%, nfe) (gnomAD).

AGL p.Ile9fs

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.24_25del · rs1648909681 · VCV976686

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

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	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 34
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.9	GERP 1.6, 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) · 2/1,179,940 alleles

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

Overall 0.000137% 2/1,461,720 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.Ile9fs
Coding: c.24_25del
MANE Select: NM_000642
dbSNP: rs1648909681
Type: Deletion
Location: chr1:99851066 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.88 · 1 PDB
Residue 9: the 'amylo-1,6-glucosidase' region; a β-strand

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.Ile9Val Uncertain significance ★ ⚠ same residue
AGL c.293+1del Pathogenic/Likely pathogenic ★★ same condition
AGL c.3481_3589-407del Pathogenic ★★ same condition
AGL c.3588_3588+14del Pathogenic/Likely pathogenic ★★ same condition
AGL p.Ala117fs Pathogenic ★★ same condition
AGL p.Ala1222fs Pathogenic ★★ same condition
AGL p.Ala1388_Pro1389insTer Pathogenic/Likely pathogenic ★★ same condition
AGL p.Ala1400fs 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-ile9fs (accessed [today's date]).

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