NR2E3 p.Pro91=
c.273C>T · rs773837062 · VCV1077277
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0219%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -12 | GERP -4 |
| Overall | ||
| CADD | 0.755 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0219%
African / African-American · 16/73,032 alleles
Filtering AF
0.0137%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0111%
Overall
0.00271%
42/1,551,146 alleles · ultra-rare
exomes 30/1,399,008 · genomes 12/152,138 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0219% | 4,565 |
| East Asian | 0.0147% | 6,820 |
| Remaining individualsnot grpmax-eligible | 0.00333% | 30,046 |
| European (non-Finnish) | 0.00157% | 63,720 |
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.Pro91=
- Coding
- c.273C>T
- MANE Select
- NM_014249
- dbSNP
- rs773837062
- Type
- single nucleotide variant
- Location
- chr15:71811793 (GRCh38)
- Gene constraint
- LOEUF 1.47 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.59 · 1 PDB
- Residue 91
- a DNA-binding region
Similar variants
- 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
- NR2E3 c.349+5G>C Pathogenic/Likely pathogenic ★★ same type
- NR2E3 c.748-1G>A Likely pathogenic ★★ same type
- NR2E3 p.Ala102Asp Pathogenic/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-pro91 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown