Is AGL p.Pro891fs (c.2670del) pathogenic?

AGL p.Pro891fs (c.2670del) is classified Pathogenic/Likely pathogenic in AGL (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-09-05). Very rare (popmax 0.00267%, afr); Associated with glycogen storage disease III.

What condition is associated with AGL p.Pro891fs (c.2670del)?

AGL p.Pro891fs (c.2670del) is associated with glycogen storage disease III (ClinVar).

How common is AGL p.Pro891fs (c.2670del) in the general population?

AGL p.Pro891fs (c.2670del) is very rare (popmax 0.00267%, afr) (gnomAD).

AGL p.Pro891fs

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.2670del · rs764591009 · VCV546284

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

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 20 of 34
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.2	GERP -3.4, phastCons 0.98
Overall
CADD	27.8	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 0.00267% African / African-American · 2/74,926 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,613,860 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.Pro891fs
Coding: c.2670del
MANE Select: NM_000642
dbSNP: rs764591009
Type: Deletion
Location: chr1:99884691 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.88 · 1 PDB
Residue 891: 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.Pro891Ser Uncertain significance ★ ⚠ same residue
AGL p.Pro891= 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

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-pro891fs (accessed [today's date]).

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