Is AGL p.Arg34Ter (c.100C>T) pathogenic?

AGL p.Arg34Ter (c.100C>T) is classified Pathogenic/Likely pathogenic in AGL (ClinVar, Multiple submitters, 13 submitters; last evaluated 2025-10-28). Very rare (popmax 0.00669%, eas); Associated with AGL-related disorder.

What condition is associated with AGL p.Arg34Ter (c.100C>T)?

AGL p.Arg34Ter (c.100C>T) is associated with AGL-related disorder, glycogen storage disease III (ClinVar).

How common is AGL p.Arg34Ter (c.100C>T) in the general population?

AGL p.Arg34Ter (c.100C>T) is very rare (popmax 0.00669%, eas) (gnomAD).

AGL p.Arg34Ter

c.100C>T · rs781580050 · VCV188743

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Conditions

AGL-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 34
Splicing
SpliceAI	Δ0.64	acceptor gain · deltas
Pangolin	Δ0.27	gain · loss 0.15 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.6	GERP 0.5, phastCons 1
Overall
CADD	46.0	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 0.00669% East Asian · 3/44,840 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000992% 16/1,613,670 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,947
South Asian	0.0022%	45,535
Admixed American	0.00167%	59,990
Remaining individualsnot grpmax-eligible	0.0016%	62,462
European (non-Finnish)	0.000763%	131,096

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.Arg34Ter
Coding: c.100C>T
MANE Select: NM_000642
dbSNP: rs781580050
Type: single nucleotide variant
Location: chr1:99861520 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.88 · 1 PDB
Residue 34: the 'amylo-1,6-glucosidase' region; a β-strand

Full AGL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

AGL-related disorder

Also linked: glycogen storage disease III

Similar variants

AGL p.Arg34Gln Uncertain significance ★ ⚠ same residue
AGL p.Arg34= Likely benign ★ same residue
AGL p.Arg34fs Pathogenic ★ same residue
AGL p.Arg34Pro 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

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-arg34ter (accessed [today's date]).

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