Is AGXT p.Val326fs (c.976del) pathogenic?

AGXT p.Val326fs (c.976del) is classified Pathogenic in AGXT (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-06-03). Very rare (popmax 0.000169%, nfe); Associated with primary hyperoxaluria.

What condition is associated with AGXT p.Val326fs (c.976del)?

AGXT p.Val326fs (c.976del) is associated with primary hyperoxaluria, primary hyperoxaluria type 1 (ClinVar).

How common is AGXT p.Val326fs (c.976del) in the general population?

AGXT p.Val326fs (c.976del) is very rare (popmax 0.000169%, nfe) (gnomAD).

How is Primary hyperoxaluria inherited?

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

AGXT p.Val326fs

c.976del · rs180177301 · VCV189161

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

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 10 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -20	GERP -2.3

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,020 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,460,694 alleles · very rare

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.Val326fs
Coding: c.976del
MANE Select: NM_000030
dbSNP: rs180177301
Type: Deletion
Location: chr2:240878055 (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 326: a UniProt-annotated variant site (in)

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 p.Val326Ile Benign ★★ ⚠ same residue
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

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-val326fs (accessed [today's date]).

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