Is NCOR2 p.Ser2197= (c.6591C>T) pathogenic?

NCOR2 p.Ser2197= (c.6591C>T) is classified Benign in NCOR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-12). Low-frequency (popmax 2.5%, afr); Associated with NCOR2-related disorder.

What condition is associated with NCOR2 p.Ser2197= (c.6591C>T)?

NCOR2 p.Ser2197= (c.6591C>T) is associated with NCOR2-related disorder (ClinVar).

How common is NCOR2 p.Ser2197= (c.6591C>T) in the general population?

NCOR2 p.Ser2197= (c.6591C>T) is low-frequency (popmax 2.5%, afr) (gnomAD).

NCOR2 p.Ser2197=

c.6591C>T · rs181072341 · VCV3033094

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 2.5%, afr)

Conditions

NCOR2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.295	indeterminate
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.5	GERP -3.1
Overall
CADD	3.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.5% African / African-American · 1,732/69,276 alleles

Filtering AF 2.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.36%

Overall 0.133% 1,997/1,502,384 alleles · low-frequency exomes 826/1,350,128 · genomes 1,171/152,256 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.5%	40
Remaining individualsnot grpmax-eligible	0.209%	480
Admixed American	0.182%	551
Middle Eastern	0.0709%	1,410
South Asian	0.0295%	3,392
European (non-Finnish)	0.00363%	27,515

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.Ser2197=
Coding: c.6591C>T
MANE Select: NM_006312
dbSNP: rs181072341
Type: single nucleotide variant
Location: chr12:124334438 (GRCh38)
Gene constraint: LOEUF 0.448 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 41.00 · 36 PDB
Residue 2197: 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-ser2197 (accessed [today's date]).

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