Is NCOR2 p.Ser750= (c.2250C>T) pathogenic?

NCOR2 p.Ser750= (c.2250C>T) is classified Likely benign in NCOR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-14). Rare (popmax 0.212%, afr); Associated with NCOR2-related disorder.

What condition is associated with NCOR2 p.Ser750= (c.2250C>T)?

NCOR2 p.Ser750= (c.2250C>T) is associated with NCOR2-related disorder (ClinVar).

How common is NCOR2 p.Ser750= (c.2250C>T) in the general population?

NCOR2 p.Ser750= (c.2250C>T) is rare (popmax 0.212%, afr) (gnomAD).

NCOR2 p.Ser750=

c.2250C>T · rs199707896 · VCV3042348

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.212%, afr)

Conditions

NCOR2-related disorder

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 0.53	GERP -1, phastCons 0.003
Overall
CADD	5.566	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.212% African / African-American · 159/74,962 alleles

Filtering AF 0.185% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.175%

Overall 0.0161% 257/1,598,348 alleles · rare exomes 132/1,446,140 · genomes 125/152,208 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.212%	471
Ashkenazi Jewishnot grpmax-eligible	0.0372%	2,686
Middle Eastern	0.033%	3,028
Admixed American	0.025%	3,997
Remaining individualsnot grpmax-eligible	0.0208%	4,798
European (non-Finnish)	0.00483%	20,695

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.Ser750=
Coding: c.2250C>T
MANE Select: NM_006312
dbSNP: rs199707896
Type: single nucleotide variant
Location: chr12:124372579 (GRCh38)
Gene constraint: LOEUF 0.448 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 41.00 · 36 PDB
Residue 750: a modified residue (phosphoserine); the 'disordered' region

Full NCOR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

NCOR2-related disorder

Similar variants

NCOR2 p.Ala1526Thr Uncertain significance ★★ ⚠ same condition
NCOR2 p.Arg2467Gln Uncertain significance ★★ ⚠ same condition
NCOR2 c.1329-4G>A Benign same condition
NCOR2 c.3242-9G>A Benign same condition
NCOR2 c.6411+8C>T Likely benign same condition
NCOR2 c.7364-5C>T Likely benign same condition
NCOR2 c.-6A>C Likely benign same condition
NCOR2 p.Ala1037= Benign 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/ncor2-p-ser750 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown