Is AGL p.Asp501fs (c.1497_1500dup) pathogenic?

AGL p.Asp501fs (c.14971500dup) is classified Pathogenic in AGL (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-21). Very rare (popmax 0.0022%, sas); Associated with disorder of glycogen metabolism.

What condition is associated with AGL p.Asp501fs (c.1497_1500dup)?

AGL p.Asp501fs (c.1497_1500dup) is associated with disorder of glycogen metabolism, glycogen storage disease III (ClinVar).

How common is AGL p.Asp501fs (c.1497_1500dup) in the general population?

AGL p.Asp501fs (c.1497_1500dup) is very rare (popmax 0.0022%, sas) (gnomAD).

AGL p.Asp501fs

c.1497_1500dup · rs1204840140 · VCV973525

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

disorder of glycogen metabolism

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 12 of 34
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 1.7, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,066 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000137% 2/1,461,752 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.Asp501fs
Coding: c.1497_1500dup
MANE Select: NM_000642
dbSNP: rs1204840140
Type: Microsatellite
Location: chr1:99877713 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.88 · 1 PDB
Residue 501: 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

disorder of glycogen metabolism — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: glycogen storage disease III

Similar variants

AGL p.Asp501= Likely benign ★ same residue
AGL p.Arg784fs Pathogenic/Likely pathogenic ★★ same condition
AGL p.Glu1072fs Pathogenic ★★ same condition
AGL p.Glu1076fs Pathogenic/Likely pathogenic ★★ same condition
AGL p.Gly1273fs Pathogenic/Likely pathogenic ★★ same condition
AGL p.Ser1323_Tyr1324insTer Pathogenic ★★ same condition
AGL p.Tyr1068_Arg1069delinsTer Pathogenic ★★ same condition
AGL p.Val127fs 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-asp501fs (accessed [today's date]).

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