Is OXGR1 p.Ser233Arg (c.697A>C) pathogenic?

OXGR1 p.Ser233Arg (c.697A>C) is classified Uncertain significance in OXGR1 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-12-20). AlphaMissense: likely benign (0.1586); Ultra-rare (popmax 0.0116%, nfe); Associated with nephrolithiasis, calcium oxalate, 2, with or without nephrocalcinosis.

What condition is associated with OXGR1 p.Ser233Arg (c.697A>C)?

OXGR1 p.Ser233Arg (c.697A>C) is associated with nephrolithiasis, calcium oxalate, 2, with or without nephrocalcinosis (ClinVar).

How common is OXGR1 p.Ser233Arg (c.697A>C) in the general population?

OXGR1 p.Ser233Arg (c.697A>C) is ultra-rare (popmax 0.0116%, nfe) (gnomAD).

What do computational predictors say about OXGR1 p.Ser233Arg (c.697A>C)?

AlphaMissense predicts likely benign (score 0.1586) — an in-silico prediction, not a clinical call.

OXGR1 p.Ser233Arg

c.697A>C · rs377575938 · VCV2404574

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1586 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0116%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nephrolithiasis, calcium oxalate, 2, with or without nephrocalcinosis

Computational evidence

Protein change
AlphaMissense	0.1586	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -5.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 1.3, phastCons 0.98
Regional constraint	o/e 0.98	unconstrained · MANE · 1,010 bp · p 0.64 · regional, not allelic
Overall
CADD	16.99	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0116% European (non-Finnish) · 137/1,180,048 alleles

Filtering AF 0.01% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00939%

Overall 0.00874% 141/1,614,134 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0116%	8,613
Remaining individualsnot grpmax-eligible	0.0064%	15,623

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: OXGR1
Protein: p.Ser233Arg
Coding: c.697A>C
MANE Select: NM_001346194
dbSNP: rs377575938
Type: single nucleotide variant
Location: chr13:96987063 (GRCh38)
Gene constraint: LOEUF 1.504 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.61 · 17 PDB
Residue 233: a UniProt-annotated variant site (in caon2; uncertain significance; loss of alpha-ketoglutarate-dependent g protein-coupled receptor activity at ph 5 but not at ph 7 when expressed in a heterologous system)

Full OXGR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nephrolithiasis, calcium oxalate, 2, with or without nephrocalcinosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

OXGR1 p.Leu124Arg Likely pathogenic ★ same condition
OXGR1 p.Leu75Met Uncertain significance ★ ⚠ same condition
OXGR1 p.Cys217Arg Pathogenic same condition
OXGR1 p.Val46Met Likely pathogenic ⚠ same condition
OXGR1 p.Ser56fs Pathogenic same condition
OXGR1 p.Ser140Thr Uncertain significance ★★ ⚠ same type
OXGR1 p.Ala155Val Uncertain significance ★ ⚠ same type
OXGR1 p.Ala76Val Uncertain significance ★ ⚠ same type

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/oxgr1-p-ser233arg (accessed [today's date]).

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