NR2E3 p.Pro280=
c.840G>A · rs1409384602 · VCV1103762
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0329%, mid)
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 -6.5 | GERP -3.7 |
| Overall | ||
| CADD | 0.081 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0329%
Middle Eastern · 2/6,078 alleles
Filtering AF
0.0058%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00241%
Overall
0.000621%
10/1,610,344 alleles · ultra-rare
exomes 8/1,458,130 · genomes 2/152,214 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0329% | 3,039 |
| African / African-American | 0.00267% | 37,441 |
| European (non-Finnish) | 0.000509% | 196,417 |
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
- NR2E3
- Protein
- p.Pro280=
- Coding
- c.840G>A
- MANE Select
- NM_014249
- dbSNP
- rs1409384602
- Type
- single nucleotide variant
- Location
- chr15:71813481 (GRCh38)
- Gene constraint
- LOEUF 1.47 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.59 · 1 PDB
- Residue 280
- the nr lbd domain
Similar variants
- NR2E3 p.Pro280Leu Uncertain significance ★★ ⚠ same residue
- NR2E3 p.Pro280Ala Uncertain significance ★ ⚠ same residue
- NR2E3 p.Pro280fs Pathogenic ★ same residue
- NR2E3 c.118+1G>T Likely pathogenic ★★ same type
- NR2E3 c.119-2A>C Pathogenic/Likely pathogenic ★★ same type
- NR2E3 c.119-2A>G Pathogenic ★★ same type
- NR2E3 c.119-2A>T Pathogenic/Likely pathogenic ★★ same type
- NR2E3 c.246-1G>C Likely pathogenic ★★ 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/nr2e3-p-pro280 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown