Is AGL c.293+1del pathogenic?

AGL c.293+1del is classified Pathogenic/Likely pathogenic in AGL (ClinVar, Multiple submitters, 9 submitters; last evaluated 2025-11-25). Very rare (popmax 0.00237%, nfe); Associated with glycogen storage disease III.

What condition is associated with AGL c.293+1del?

AGL c.293+1del is associated with glycogen storage disease III, disorder of glycogen metabolism (ClinVar).

How common is AGL c.293+1del in the general population?

AGL c.293+1del is very rare (popmax 0.00237%, nfe) (gnomAD).

AGL c.293+1del

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.

rs777857395 · VCV370565

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00237%, nfe)

Conditions

glycogen storage disease III

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +1	canonical splice dinucleotide (donor +1) · inside the BP7-excluded zone
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.6	GERP -1.1, phastCons 1
Non-coding constraint	Z -0.28	1 kb window · o/e 1.02 · regional · uncalibrated
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 0.00237% European (non-Finnish) · 28/1,179,678 alleles

Filtering AF 0.00165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00198% 32/1,613,394 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,229
European (non-Finnish)grpmax	0.00237%	42,131
Admixed American	0.00167%	59,998
African / African-American	0.00133%	74,914

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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
Coding: c.293+1del
MANE Select: NM_000642
dbSNP: rs777857395
Type: Deletion
Location: chr1:99861712 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.88 · 1 PDB

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

Also linked: disorder of glycogen metabolism

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 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
AGL p.Ala1475fs Pathogenic/Likely pathogenic ★★ same condition
AGL p.Arg610fs 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-c-293-plus-1del (accessed [today's date]).

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