Is NR0B2 p.Arg34Pro (c.101G>C) pathogenic?

NR0B2 p.Arg34Pro (c.101G>C) is classified Uncertain significance in NR0B2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-10). AlphaMissense: likely benign (0.0602); Absent from gnomAD v4.1; Associated with NR0B2-related disorder.

What condition is associated with NR0B2 p.Arg34Pro (c.101G>C)?

NR0B2 p.Arg34Pro (c.101G>C) is associated with NR0B2-related disorder (ClinVar).

How common is NR0B2 p.Arg34Pro (c.101G>C) in the general population?

NR0B2 p.Arg34Pro (c.101G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NR0B2 p.Arg34Pro (c.101G>C)?

AlphaMissense predicts likely benign (score 0.0602) — an in-silico prediction, not a clinical call.

NR0B2 p.Arg34Pro

c.101G>C · rs759817886 · VCV2628653

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0602 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

NR0B2-related disorder

Computational evidence

Protein change
AlphaMissense	0.0602	likely benign
REVEL	0.235	benign-leaning
SaProt	LLR -6.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.20	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 1.6	GERP -3.6, phastCons 0.35
Regional constraint	o/e 0.94	unconstrained · MANE · 2,092 bp · p 0.24 · regional, not allelic
Overall
CADD	8.851	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NR0B2
Protein: p.Arg34Pro
Coding: c.101G>C
MANE Select: NM_021969
dbSNP: rs759817886
Type: single nucleotide variant
Location: chr1:26913840 (GRCh38)
Gene constraint: LOEUF 1.34 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.42 · 14 PDB
Residue 34: the nr lbd domain

Full NR0B2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

NR0B2-related disorder

Similar variants

NR0B2 p.Arg34Gln Uncertain significance ⚠ same residue
NR0B2 p.Arg34Gly Uncertain significance ★ ⚠ same residue
NR0B2 p.Arg34Ter Pathogenic same residue
NR0B2 p.Asp245Gly Uncertain significance ★★ ⚠ same condition
NR0B2 p.Ala209Thr Uncertain significance ★ ⚠ same condition
NR0B2 p.Ala31Thr Uncertain significance ★ ⚠ same condition
NR0B2 p.Arg257Gly Uncertain significance ★ ⚠ same condition
NR0B2 p.Arg86Gln Uncertain significance ★ ⚠ 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/nr0b2-p-arg34pro (accessed [today's date]).

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