NR2E3 p.Ser44=
c.132G>A · rs759064828 · VCV1156935
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00547%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.53 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.2 | GERP -3 |
| Overall | ||
| CADD | 6.478 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00547%
European (non-Finnish) · 63/1,152,644 alleles
Filtering AF
0.00436%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00397%
Overall
0.00474%
74/1,559,704 alleles · very rare
exomes 66/1,407,648 · genomes 8/152,056 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00547% | 18,296 |
| South Asian | 0.00473% | 21,151 |
| African / African-American | 0.00409% | 24,436 |
| Remaining individualsnot grpmax-eligible | 0.00331% | 30,231 |
| East Asian | 0.00241% | 41,452 |
| Admixed American | 0.00194% | 51,550 |
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.Ser44=
- Coding
- c.132G>A
- MANE Select
- NM_014249
- dbSNP
- rs759064828
- Type
- single nucleotide variant
- Location
- chr15:71811496 (GRCh38)
- Gene constraint
- LOEUF 1.47 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.59 · 1 PDB
- Residue 44
- a UniProt-annotated variant site (in rp37; uncertain significance); a DNA-binding region
Similar variants
- NR2E3 p.Ser44Ter Pathogenic ★★ same residue
- NR2E3 p.Ser44Leu 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-ser44 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown