Is NCOR2 p.Ala2191= (c.6573C>G) pathogenic?

NCOR2 p.Ala2191= (c.6573C>G) is classified Likely benign in NCOR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-08). Rare (popmax 0.193%, nfe); Associated with NCOR2-related disorder.

What condition is associated with NCOR2 p.Ala2191= (c.6573C>G)?

NCOR2 p.Ala2191= (c.6573C>G) is associated with NCOR2-related disorder (ClinVar).

How common is NCOR2 p.Ala2191= (c.6573C>G) in the general population?

NCOR2 p.Ala2191= (c.6573C>G) is rare (popmax 0.193%, nfe) (gnomAD).

NCOR2 p.Ala2191=

c.6573C>G · rs201853086 · VCV3033778

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.193%, nfe)

Conditions

NCOR2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.04	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.7	GERP -3.1, phastCons 1
Overall
CADD	5.082	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.193% European (non-Finnish) · 2,175/1,126,786 alleles

Filtering AF 0.186% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.184%

Overall 0.161% 2,420/1,498,646 alleles · rare exomes 2,200/1,346,344 · genomes 220/152,302 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.193%	518
Finnishnot grpmax-eligible	0.183%	547
Admixed American	0.151%	661
Remaining individualsnot grpmax-eligible	0.0978%	1,023
African / African-American	0.0231%	4,335
Ashkenazi Jewishnot grpmax-eligible	0.00403%	24,794
South Asian	0.00131%	76,420

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.Ala2191=
Coding: c.6573C>G
MANE Select: NM_006312
dbSNP: rs201853086
Type: single nucleotide variant
Location: chr12:124334456 (GRCh38)
Gene constraint: LOEUF 0.448 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 41.00 · 36 PDB
Residue 2191: 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-ala2191 (accessed [today's date]).

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