Is AGXT p.Leu43fs (c.126del) pathogenic?

AGXT p.Leu43fs (c.126del) is classified Pathogenic/Likely pathogenic in AGXT (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-20). Very rare (popmax 0.00476%, eas); Associated with primary hyperoxaluria.

What condition is associated with AGXT p.Leu43fs (c.126del)?

AGXT p.Leu43fs (c.126del) is associated with primary hyperoxaluria, primary hyperoxaluria type 1 (ClinVar).

How common is AGXT p.Leu43fs (c.126del) in the general population?

AGXT p.Leu43fs (c.126del) is very rare (popmax 0.00476%, eas) (gnomAD).

How is Primary hyperoxaluria inherited?

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

AGXT p.Leu43fs

c.126del · rs180177171 · VCV204176

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00476%, eas)

Conditions

primary hyperoxaluria

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 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -20	GERP -2.5

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00476% East Asian · 2/41,988 alleles

Filtering AF 0.000789% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000295%

Overall 0.000284% 4/1,408,406 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00476%	20,994
Remaining individualsnot grpmax-eligible	0.0017%	58,962
European (non-Finnish)	8.83e-05%	1,132,128

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: AGXT
Protein: p.Leu43fs
Coding: c.126del
MANE Select: NM_000030
dbSNP: rs180177171
Type: Deletion
Location: chr2:240868986 (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 43: an α-helix

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

Disease context

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

Also linked: primary hyperoxaluria type 1

For Primary hyperoxaluria (Orphanet):

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

Similar variants

AGXT c.359-1_382del Pathogenic ★★ same condition
AGXT c.424-66_425del Likely pathogenic ★★ same condition
AGXT c.679_680+2del Pathogenic ★★ same condition
AGXT p.Ala325fs Pathogenic/Likely pathogenic ★★ same condition
AGXT p.Gln110fs Pathogenic ★★ same condition
AGXT p.Gln145fs Pathogenic/Likely pathogenic ★★ same condition
AGXT p.Leu151fs Pathogenic ★★ same condition
AGXT p.Leu193fs 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-leu43fs (accessed [today's date]).

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