NR2E3 p.Val85=
c.255G>C · rs374027410 · VCV1086674
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000872%, nfe)
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 -0.54 | GERP -3.2, phastCons 0.002 |
| Overall | ||
| CADD | 4.061 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000872%
European (non-Finnish) · 10/1,146,560 alleles
Filtering AF
0.000441%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000322%
Overall
0.000645%
10/1,550,794 alleles · very rare
exomes 10/1,398,488 · genomes 0/152,306 · joint denominator
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.Val85=
- Coding
- c.255G>C
- MANE Select
- NM_014249
- dbSNP
- rs374027410
- Type
- single nucleotide variant
- Location
- chr15:71811775 (GRCh38)
- Gene constraint
- LOEUF 1.47 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.59 · 1 PDB
- Residue 85
- a DNA-binding region
Similar variants
- NR2E3 p.Val85Leu Uncertain significance ★★ ⚠ same residue
- NR2E3 p.Val85Met Uncertain significance ★★ ⚠ 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
- NR2E3 c.349+5G>C 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-val85 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown