NCOR2 p.Ile281=
c.843C>T · rs374551612 · VCV2643563
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.225%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.013 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.8 | GERP -3.9, phastCons 0.97 |
| Overall | ||
| CADD | 8.172 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.225%
European (non-Finnish) · 2,652/1,179,260 alleles
Filtering AF
0.218%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.215%
Overall
0.18%
2,908/1,612,350 alleles · rare
exomes 2,720/1,460,176 · genomes 188/152,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.225% | 445 |
| Finnishnot grpmax-eligible | 0.171% | 586 |
| Remaining individualsnot grpmax-eligible | 0.141% | 709 |
| Admixed American | 0.0668% | 1,496 |
| Middle Eastern | 0.0329% | 3,037 |
| African / African-American | 0.0214% | 4,681 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,562 |
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.Ile281=
- Coding
- c.843C>T
- MANE Select
- NM_006312
- dbSNP
- rs374551612
- Type
- single nucleotide variant
- Location
- chr12:124437969 (GRCh38)
- Gene constraint
- LOEUF 0.448 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 41.00 · 36 PDB
- Residue 281
- the 'interaction with sin3a/b' region
Similar variants
- 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
- NCOR2 p.Ala1699Thr 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-ile281 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown