Is AGXT p.Arg360Trp (c.1078C>T) pathogenic?

AGXT p.Arg360Trp (c.1078C>T) is classified Pathogenic/Likely pathogenic in AGXT (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-09). AlphaMissense: likely pathogenic (0.6234); Very rare (popmax 0.00471%, eas); Associated with primary hyperoxaluria type 1.

What condition is associated with AGXT p.Arg360Trp (c.1078C>T)?

AGXT p.Arg360Trp (c.1078C>T) is associated with primary hyperoxaluria type 1 (ClinVar).

How common is AGXT p.Arg360Trp (c.1078C>T) in the general population?

AGXT p.Arg360Trp (c.1078C>T) is very rare (popmax 0.00471%, eas) (gnomAD).

How is Primary hyperoxaluria inherited?

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

What do computational predictors say about AGXT p.Arg360Trp (c.1078C>T)?

AlphaMissense predicts likely pathogenic (score 0.6234) — an in-silico prediction, not a clinical call.

AGXT p.Arg360Trp

c.1078C>T · rs758493460 · VCV2203299

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.6234 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00471%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary hyperoxaluria type 1

Computational evidence

Protein change
AlphaMissense	0.6234	likely pathogenic ✓ concordant with ClinVar
REVEL	0.906	moderately pathogenic-leaning
SaProt	LLR -15.86	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 5.8	GERP 1.3, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 9,952 bp · p 0.92 · regional, not allelic
Overall
CADD	28.6	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

Grpmax group 0.00471% East Asian · 2/42,506 alleles

Filtering AF 0.00078% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000292%

Overall 0.000853% 12/1,406,356 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00471%	21,253
Finnishnot grpmax-eligible	0.00187%	53,338
Remaining individualsnot grpmax-eligible	0.00165%	60,700
African / African-American	0.00135%	74,190
European (non-Finnish)	0.000606%	165,079

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.Arg360Trp
Coding: c.1078C>T
MANE Select: NM_000030
dbSNP: rs758493460
Type: single nucleotide variant
Location: chr2:240878720 (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 360: a binding site; a β-strand

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 p.Arg360Gln Pathogenic/Likely pathogenic ★★ same residue
AGXT p.Arg360= Likely benign ★ same residue
AGXT p.Arg360Pro Likely pathogenic same residue
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

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-arg360trp (accessed [today's date]).

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