NR4A2 p.Pro349=
c.1047G>C · rs749000269 · VCV758571
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00708%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.08 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 4.1 | GERP 2.5, phastCons 1 |
| Overall | ||
| CADD | 13.72 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00708%
European (non-Finnish) · 83/1,173,080 alleles
Filtering AF
0.00583%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00536%
Overall
0.0055%
88/1,601,208 alleles · very rare
exomes 79/1,449,068 · genomes 9/152,140 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00708% | 14,133 |
| African / African-American | 0.00402% | 24,906 |
| Remaining individualsnot grpmax-eligible | 0.00323% | 30,978 |
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
- NR4A2
- Protein
- p.Pro349=
- Coding
- c.1047G>C
- MANE Select
- NM_006186
- dbSNP
- rs749000269
- Type
- single nucleotide variant
- Location
- chr2:156327962 (GRCh38)
- Gene constraint
- LOEUF 0.093 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 66.39 · 8 PDB
- Residue 349
- the 'disordered' region
Similar variants
- NR4A2 p.Arg370Lys Uncertain significance ★★ ⚠ same type
- NR4A2 p.Leu300Ser Uncertain significance ★★ ⚠ same type
- NR4A2 p.Phe287Leu Uncertain significance ★★ ⚠ same type
- NR4A2 p.Pro124= Uncertain significance ★★ same type
- NR4A2 c.-223C>T Likely benign ★★ same type
- NR4A2 c.*331T>G Benign ★★ same type
- NR4A2 p.Ile163= Benign/Likely benign ★★ same type
- NR4A2 p.Leu244= Benign/Likely benign ★★ 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/nr4a2-p-pro349 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown