Is AGL p.Arg910= (c.2728C>A) pathogenic?

AGL p.Arg910= (c.2728C>A) is classified Uncertain significance in AGL (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-03-13). Very rare (popmax 8.48e-05%, nfe); Associated with glycogen storage disease III.

What condition is associated with AGL p.Arg910= (c.2728C>A)?

AGL p.Arg910= (c.2728C>A) is associated with glycogen storage disease III (ClinVar).

How common is AGL p.Arg910= (c.2728C>A) in the general population?

AGL p.Arg910= (c.2728C>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

AGL p.Arg910=

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.2728C>A · VCV4068134

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

glycogen storage disease III

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.57	acceptor gain · deltas
Pangolin	Δ0.33	gain · loss 0.19 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Overall
CADD	20.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,580 alleles

Overall 6.84e-05% 1/1,461,154 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.Arg910=
Coding: c.2728C>A
MANE Select: NM_000642
Type: single nucleotide variant
Location: chr1:99888024 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.88 · 1 PDB
Residue 910: 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.Arg910Ter Pathogenic ★★ same residue
AGL p.Arg910Gln Uncertain significance ★★ ⚠ same residue
AGL p.Arg910Leu Uncertain significance ★ ⚠ same residue
AGL c.1283+2T>C Likely pathogenic ★★ same condition
AGL c.1284-1G>A Likely pathogenic ★★ same condition
AGL c.1284-2A>G Likely pathogenic ★★ same condition
AGL c.1423+1G>A Pathogenic ★★ same condition
AGL c.1423+1G>C 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-arg910 (accessed [today's date]).

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