Is AGA p.Ile240fs (c.716dup) pathogenic?

AGA p.Ile240fs (c.716dup) is classified Likely pathogenic in AGA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-25). Associated with aspartylglucosaminuria.

What condition is associated with AGA p.Ile240fs (c.716dup)?

AGA p.Ile240fs (c.716dup) is associated with aspartylglucosaminuria (ClinVar).

How is Aspartylglucosaminuria inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

AGA p.Ile240fs

c.716dup · VCV4817938

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

aspartylglucosaminuria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -5.1	GERP -3

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: AGA
Protein: p.Ile240fs
Coding: c.716dup
MANE Select: NM_000027
Type: Duplication
Location: chr4:177434471 (GRCh38)
Gene constraint: LOEUF 0.938 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.41 · 2 PDB

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

Disease context

aspartylglucosaminuria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Aspartylglucosaminuria (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Australia)

Similar variants

AGA p.Ile240Thr Uncertain significance ★ ⚠ same residue
AGA p.Met63fs Pathogenic ★★ same condition
AGA p.Pro268fs Pathogenic/Likely pathogenic ★★ same condition
AGA c.394+10dup Benign/Likely benign ★★ same condition
AGA p.Asn170fs Pathogenic ★ same condition
AGA p.Asp174fs Pathogenic ★ same condition
AGA p.Leu267fs Pathogenic ★ same condition
AGA p.Met90fs 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/aga-p-ile240fs (accessed [today's date]).

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