NCOR2 p.Pro1409=
c.4227G>A · rs768218509 · VCV3047009
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0168%, mid)
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 -3.8 |
| Overall | ||
| CADD | 1.95 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0168%
Middle Eastern · 1/5,942 alleles
Filtering AF
0.00349%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00239%
Overall
0.00153%
24/1,572,078 alleles · ultra-rare
exomes 18/1,419,730 · genomes 6/152,348 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0168% | 5,942 |
| African / African-American | 0.00805% | 12,424 |
| East Asian | 0.00692% | 14,441 |
| Admixed American | 0.0056% | 17,849 |
| South Asian | 0.00349% | 28,630 |
| Remaining individualsnot grpmax-eligible | 0.00164% | 60,998 |
| European (non-Finnish) | 0.000603% | 165,754 |
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
- NCOR2
- Protein
- p.Pro1409=
- Coding
- c.4227G>A
- MANE Select
- NM_006312
- dbSNP
- rs768218509
- Type
- single nucleotide variant
- Location
- chr12:124346696 (GRCh38)
- Gene constraint
- LOEUF 0.448 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 41.00 · 36 PDB
Similar variants
- NCOR2 p.Pro1409Leu Uncertain significance ★ ⚠ same residue
- NCOR2 p.Ala1526Thr Uncertain significance ★★ ⚠ same type
- NCOR2 p.Arg2174Cys Uncertain significance ★★ ⚠ same type
- NCOR2 p.Arg2467Gln Uncertain significance ★★ ⚠ same type
- NCOR2 p.Gly1520Ser Uncertain significance ★★ ⚠ same type
- NCOR2 c.3986-17C>T Benign ★★ same type
- NCOR2 c.6265+16T>C Benign ★★ same type
- NCOR2 c.-36G>C Benign ★★ 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/ncor2-p-pro1409 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown