Is NR4A2 p.Pro197= (c.591C>A) pathogenic?

NR4A2 p.Pro197= (c.591C>A) is classified Uncertain significance in NR4A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-02-02). Absent from gnomAD v4.1; Associated with late-onset Parkinson disease.

What condition is associated with NR4A2 p.Pro197= (c.591C>A)?

NR4A2 p.Pro197= (c.591C>A) is associated with late-onset Parkinson disease (ClinVar).

How common is NR4A2 p.Pro197= (c.591C>A) in the general population?

NR4A2 p.Pro197= (c.591C>A) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary late-onset Parkinson disease inherited?

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

NR4A2 p.Pro197=

c.591C>A · rs769738246 · VCV894758

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

late-onset Parkinson disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.064	GERP -4.4, phastCons 0.52
Overall
CADD	8.961	PHRED · no single calibrated threshold — expert panels disagree

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: NR4A2
Protein: p.Pro197=
Coding: c.591C>A
MANE Select: NM_006186
dbSNP: rs769738246
Type: single nucleotide variant
Location: chr2:156329596 (GRCh38)
Gene constraint: LOEUF 0.093 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.39 · 8 PDB

Full NR4A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

late-onset Parkinson disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary late-onset Parkinson disease (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

NR4A2 p.Pro124= Uncertain significance ★★ same condition
NR4A2 c.-223C>T Likely benign ★★ same condition
NR4A2 c.*331T>G Benign ★★ same condition
NR4A2 p.Leu244= Benign/Likely benign ★★ same condition
NR4A2 p.Cys299Phe Pathogenic ★ same condition
NR4A2 c.1158+13C>T Uncertain significance ★ same condition
NR4A2 c.-144G>A Uncertain significance ★ same condition
NR4A2 c.-166C>G 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/nr4a2-p-pro197 (accessed [today's date]).

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