Is AGL p.Pro842fs (c.2520_2524dup) pathogenic?

AGL p.Pro842fs (c.25202524dup) is classified Pathogenic in AGL (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-17). Very rare (popmax 0.00223%, eas); Associated with glycogen storage disease III.

What condition is associated with AGL p.Pro842fs (c.2520_2524dup)?

AGL p.Pro842fs (c.2520_2524dup) is associated with glycogen storage disease III (ClinVar).

How common is AGL p.Pro842fs (c.2520_2524dup) in the general population?

AGL p.Pro842fs (c.2520_2524dup) is very rare (popmax 0.00223%, eas) (gnomAD).

AGL p.Pro842fs

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.2520_2524dup · rs759727721 · VCV1438378

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 19 of 34
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,812 alleles

Overall 0.000657% 1/152,180 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.Pro842fs
Coding: c.2520_2524dup
MANE Select: NM_000642
dbSNP: rs759727721
Type: Duplication
Location: chr1:99884424 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.88 · 1 PDB
Residue 842: 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.Pro842= 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-pro842fs (accessed [today's date]).

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