Is AGA p.Trp34fs (c.101_107del) pathogenic?

AGA p.Trp34fs (c.101107del) is classified Pathogenic in AGA (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-14). Very rare (popmax 0.00212%, nfe); Associated with aspartylglucosaminuria.

What condition is associated with AGA p.Trp34fs (c.101_107del)?

AGA p.Trp34fs (c.101_107del) is associated with aspartylglucosaminuria (ClinVar).

How common is AGA p.Trp34fs (c.101_107del) in the general population?

AGA p.Trp34fs (c.101_107del) is very rare (popmax 0.00212%, nfe) (gnomAD).

How is Aspartylglucosaminuria inherited?

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

AGA p.Trp34fs

c.101_107del · rs759063638 · VCV495346

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

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 1 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4	GERP 1.7, phastCons 1
Overall
CADD	35.0	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 0.00212% European (non-Finnish) · 25/1,179,902 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00167% 27/1,613,802 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00212%	47,196
Admixed American	0.00167%	59,998
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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: AGA
Protein: p.Trp34fs
Coding: c.101_107del
MANE Select: NM_000027
dbSNP: rs759063638
Type: Deletion
Location: chr4:177442269 (GRCh38)
Gene constraint: LOEUF 0.938 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.41 · 2 PDB
Residue 34: a β-strand

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.Ala19fs Pathogenic ★★ same condition
AGA p.Asn110fs Pathogenic/Likely pathogenic ★★ same condition
AGA p.Cys64fs Pathogenic/Likely pathogenic ★★ same condition
AGA p.Glu199fs Likely pathogenic ★★ same condition
AGA p.Ile112fs Pathogenic/Likely pathogenic ★★ same condition
AGA p.Lys288_Val289insTer Pathogenic/Likely pathogenic ★★ same condition
AGA p.Thr123fs Pathogenic/Likely pathogenic ★★ same condition
AGA p.Thr125_Leu126insTer 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/aga-p-trp34fs (accessed [today's date]).

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