Is AGXT p.Leu90fs (c.268dup) pathogenic?

AGXT p.Leu90fs (c.268dup) is classified Likely pathogenic in AGXT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-15). Absent from gnomAD; Associated with primary hyperoxaluria type 1.

What condition is associated with AGXT p.Leu90fs (c.268dup)?

AGXT p.Leu90fs (c.268dup) is associated with primary hyperoxaluria type 1 (ClinVar).

How common is AGXT p.Leu90fs (c.268dup) in the general population?

AGXT p.Leu90fs (c.268dup) is absent from gnomAD (gnomAD).

How is Primary hyperoxaluria inherited?

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

AGXT p.Leu90fs

c.268dup · rs2528740235 · VCV2675047

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

primary hyperoxaluria type 1

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 2 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.2	GERP 1.3, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AGXT
Protein: p.Leu90fs
Coding: c.268dup
MANE Select: NM_000030
dbSNP: rs2528740235
Type: Duplication
Location: chr2:240869269 (GRCh38)
Gene constraint: LOEUF 1.251 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 98.30 · 17 PDB
Residue 90: an α-helix

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

Disease context

primary hyperoxaluria type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary hyperoxaluria (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Germany)

Similar variants

AGXT c.166-1_172dup Pathogenic ★★ same condition
AGXT p.Ala40fs Pathogenic/Likely pathogenic ★★ same condition
AGXT p.Asp243fs Pathogenic ★★ same condition
AGXT p.Tyr270fs Pathogenic/Likely pathogenic ★★ same condition
AGXT p.Ala13fs Likely pathogenic ★ same condition
AGXT p.Asn72fs Likely pathogenic ★ same condition
AGXT p.Glu117fs Pathogenic ★ same condition
AGXT p.Leu14fs 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/agxt-p-leu90fs (accessed [today's date]).

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