Is AGXT p.Leu359Pro (c.1076T>C) pathogenic?

AGXT p.Leu359Pro (c.1076T>C) is classified Likely pathogenic in AGXT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-02-05). AlphaMissense: likely pathogenic (0.9411); Absent from gnomAD v4.1; Associated with AGXT-related disorder.

What condition is associated with AGXT p.Leu359Pro (c.1076T>C)?

AGXT p.Leu359Pro (c.1076T>C) is associated with AGXT-related disorder, primary hyperoxaluria type 1 (ClinVar).

How common is AGXT p.Leu359Pro (c.1076T>C) in the general population?

AGXT p.Leu359Pro (c.1076T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGXT p.Leu359Pro (c.1076T>C)?

AlphaMissense predicts likely pathogenic (score 0.9411) — an in-silico prediction, not a clinical call.

AGXT p.Leu359Pro

c.1076T>C · rs180177160 · VCV204146

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9411 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,557,522)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

AGXT-related disorder

Computational evidence

Protein change
AlphaMissense	0.9411	likely pathogenic ✓ concordant with ClinVar · top 3% in AGXT
REVEL	0.969	strongly pathogenic-leaning
SaProt	LLR -14.86	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.3, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 9,952 bp · p 0.92 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,557,522). 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.Leu359Pro
Coding: c.1076T>C
MANE Select: NM_000030
dbSNP: rs180177160
Type: single nucleotide variant
Location: chr2:240878718 (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 359: a β-strand

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

Disease context

AGXT-related disorder

Also linked: primary hyperoxaluria type 1

Similar variants

AGXT c.358+1G>A Pathogenic ★★ same condition
AGXT c.359-2A>G Likely pathogenic ★★ same condition
AGXT c.423+1G>A Pathogenic/Likely pathogenic ★★ same condition
AGXT c.524+2T>A Likely pathogenic ★★ same condition
AGXT c.525-1G>A Pathogenic ★★ same condition
AGXT c.525-2A>T Pathogenic/Likely pathogenic ★★ same condition
AGXT c.595+1G>T Pathogenic ★★ same condition
AGXT c.596-2A>G 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-leu359pro (accessed [today's date]).

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