NR2E3 p.Pro152=
c.456G>A · rs1192258898 · VCV991927
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0268%, eas)
Conditions
2
inherited retinal dystrophy
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 -7.4 | GERP -3 |
| Overall | ||
| CADD | 0.073 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0268%
East Asian · 11/41,012 alleles
Filtering AF
0.015%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0116%
Overall
0.00155%
24/1,552,998 alleles · ultra-rare
exomes 18/1,400,862 · genomes 6/152,136 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0268% | 3,728 |
| African / African-American | 0.00957% | 10,446 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00697% | 14,339 |
| European (non-Finnish) | 0.000348% | 287,135 |
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.Pro152=
- Coding
- c.456G>A
- MANE Select
- NM_014249
- dbSNP
- rs1192258898
- Type
- single nucleotide variant
- Location
- chr15:71812061 (GRCh38)
- Gene constraint
- LOEUF 1.47 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.59 · 1 PDB
- Residue 152
- the 'disordered' region
Similar variants
- NR2E3 p.Pro152Ser Uncertain significance ★★ ⚠ same residue
- NR2E3 p.Pro152Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- NR2E3 c.119-2A>C Pathogenic/Likely pathogenic ★★ same condition
- NR2E3 p.Ala256Glu Pathogenic/Likely pathogenic ★★ same condition
- NR2E3 p.Arg104Gln Pathogenic/Likely pathogenic ★★ same condition
- NR2E3 p.Arg122Cys Pathogenic/Likely pathogenic ★★ same condition
- NR2E3 p.Arg125Ter Pathogenic/Likely pathogenic ★★ same condition
- NR2E3 p.Arg311Gln Pathogenic/Likely pathogenic ★★ ⚠ 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/nr2e3-p-pro152 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown