Is AGL p.Ser760= (c.2280C>T) pathogenic?

AGL p.Ser760= (c.2280C>T) is classified Benign/Likely benign in AGL (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). Rare (popmax 0.816%, sas); Associated with glycogen storage disease III.

What condition is associated with AGL p.Ser760= (c.2280C>T)?

AGL p.Ser760= (c.2280C>T) is associated with glycogen storage disease III (ClinVar).

How common is AGL p.Ser760= (c.2280C>T) in the general population?

AGL p.Ser760= (c.2280C>T) is rare (popmax 0.816%, sas) (gnomAD).

AGL p.Ser760=

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.2280C>T · rs373513564 · VCV456469

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.816%, sas)

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	Δ0.91	donor gain · deltas
Pangolin	Δ0.35	gain · loss 0.20 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.1	GERP 1.9, phastCons 1
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.816% South Asian · 743/91,064 alleles

Filtering AF 0.767% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.748%

Overall 0.0506% 816/1,613,756 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.816%	123
Remaining individualsnot grpmax-eligible	0.0528%	1,894
African / African-American	0.004%	24,981
Admixed American	0.00334%	29,983
European (non-Finnish)	0.00297%	33,711

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.Ser760=
Coding: c.2280C>T
MANE Select: NM_000642
dbSNP: rs373513564
Type: single nucleotide variant
Location: chr1:99881663 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.88 · 1 PDB
Residue 760: 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.Ser760Asn Uncertain significance ★ ⚠ same residue
AGL p.Ser760fs Pathogenic ★ 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
AGL c.1423+1G>T 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-ser760 (accessed [today's date]).

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