Is AGL p.Phe694fs (c.2082_2083del) pathogenic?

AGL p.Phe694fs (c.20822083del) is classified Likely pathogenic in AGL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-04). Very rare (popmax 0.000424%, nfe); Associated with glycogen storage disease III.

What condition is associated with AGL p.Phe694fs (c.2082_2083del)?

AGL p.Phe694fs (c.2082_2083del) is associated with glycogen storage disease III (ClinVar).

How common is AGL p.Phe694fs (c.2082_2083del) in the general population?

AGL p.Phe694fs (c.2082_2083del) is very rare (popmax 0.000424%, nfe) (gnomAD).

AGL p.Phe694fs

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.2082_2083del · VCV4814436

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000424%, 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 16 of 34
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.4	GERP 0.68, phastCons 0.36

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,012 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,810 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.Phe694fs
Coding: c.2082_2083del
MANE Select: NM_000642
Type: Deletion
Location: chr1:99881372 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.88 · 1 PDB
Residue 694: 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.Phe694= Likely benign ★ 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-phe694fs (accessed [today's date]).

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