Is AGXT p.Arg317Pro (c.950G>C) pathogenic?

AGXT p.Arg317Pro (c.950G>C) is classified Uncertain significance in AGXT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-15). AlphaMissense: likely pathogenic (0.8931); Ultra-rare (popmax 0.0204%, nfe); Associated with primary hyperoxaluria type 1.

What condition is associated with AGXT p.Arg317Pro (c.950G>C)?

AGXT p.Arg317Pro (c.950G>C) is associated with primary hyperoxaluria type 1 (ClinVar).

How common is AGXT p.Arg317Pro (c.950G>C) in the general population?

AGXT p.Arg317Pro (c.950G>C) is ultra-rare (popmax 0.0204%, nfe) (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.Arg317Pro (c.950G>C)?

AlphaMissense predicts likely pathogenic (score 0.8931) — an in-silico prediction, not a clinical call.

AGXT p.Arg317Pro

c.950G>C · VCV3586231

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8931 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0204%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary hyperoxaluria type 1

Computational evidence

Protein change
AlphaMissense	0.8931	likely pathogenic · top 7% in AGXT
REVEL	0.922	moderately pathogenic-leaning
SaProt	LLR -10.49	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.39	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 8.1	GERP 1.2, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 9,952 bp · p 0.92 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0204% European (non-Finnish) · 241/1,179,992 alleles

Filtering AF 0.0182% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0174%

Overall 0.0151% 243/1,611,956 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0204%	4,896
Remaining individualsnot grpmax-eligible	0.0032%	31,244

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.Arg317Pro
Coding: c.950G>C
MANE Select: NM_000030
Type: single nucleotide variant
Location: chr2:240878029 (GRCh38)
Gene constraint: LOEUF 1.251 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 98.30 · 17 PDB

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.Arg317Gln Uncertain significance ★★ ⚠ same residue
AGXT p.Arg317Trp Conflicting classifications of pathogenicity ★ ⚠ 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
AGXT c.525-2A>T Pathogenic/Likely 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-arg317pro (accessed [today's date]).

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