Is AGL p.Arg1069Ser (c.3207G>C) pathogenic?

AGL p.Arg1069Ser (c.3207G>C) is classified Uncertain significance in AGL (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-31). AlphaMissense: ambiguous (0.4483); Absent from gnomAD v4.1; Associated with glycogen storage disease III.

What condition is associated with AGL p.Arg1069Ser (c.3207G>C)?

AGL p.Arg1069Ser (c.3207G>C) is associated with glycogen storage disease III (ClinVar).

How common is AGL p.Arg1069Ser (c.3207G>C) in the general population?

AGL p.Arg1069Ser (c.3207G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGL p.Arg1069Ser (c.3207G>C)?

AlphaMissense predicts ambiguous (score 0.4483) — an in-silico prediction, not a clinical call.

AGL p.Arg1069Ser

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.3207G>C · rs1346677449 · VCV1057946

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4483 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

glycogen storage disease III

Computational evidence

Protein change
AlphaMissense	0.4483	ambiguous
REVEL	0.469	indeterminate
SaProt	LLR -7.74	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -0.82, phastCons 0.67
Regional constraint	o/e 0.99	unconstrained · MANE · 71 kb · p 0.78 · regional, not allelic
Overall
CADD	15.24	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AGL
Protein: p.Arg1069Ser
Coding: c.3207G>C
MANE Select: NM_000642
dbSNP: rs1346677449
Type: single nucleotide variant
Location: chr1:99892555 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.88 · 1 PDB
Residue 1069: a β-strand; 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.Arg1069fs Likely 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
AGL c.1612-1G>A 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-arg1069ser (accessed [today's date]).

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