Is NCOR2 p.Glu537= (c.1611G>A) pathogenic?

NCOR2 p.Glu537= (c.1611G>A) is classified Likely benign in NCOR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-27). Rare (popmax 0.694%, mid); Associated with NCOR2-related disorder.

What condition is associated with NCOR2 p.Glu537= (c.1611G>A)?

NCOR2 p.Glu537= (c.1611G>A) is associated with NCOR2-related disorder (ClinVar).

How common is NCOR2 p.Glu537= (c.1611G>A) in the general population?

NCOR2 p.Glu537= (c.1611G>A) is rare (popmax 0.694%, mid) (gnomAD).

NCOR2 p.Glu537=

c.1611G>A · rs202047482 · VCV3055772

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.694%, mid)

Conditions

NCOR2-related disorder

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 -4.8	GERP -2.7
Overall
CADD	1.402	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.694% Middle Eastern · 42/6,056 alleles

Filtering AF 0.527% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.469%

Overall 0.0517% 834/1,614,136 alleles · rare exomes 760/1,461,806 · genomes 74/152,330 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.694%	144
Admixed American	0.128%	780
Remaining individualsnot grpmax-eligible	0.102%	977
European (non-Finnish)	0.0523%	1,912
African / African-American	0.0306%	3,263
South Asian	0.0121%	8,281

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.Glu537=
Coding: c.1611G>A
MANE Select: NM_006312
dbSNP: rs202047482
Type: single nucleotide variant
Location: chr12:124402433 (GRCh38)
Gene constraint: LOEUF 0.448 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 41.00 · 36 PDB
Residue 537: 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-glu537 (accessed [today's date]).

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