Is NCOR2 p.Arg1653= (c.4959A>G) pathogenic?

NCOR2 p.Arg1653= (c.4959A>G) is classified Benign in NCOR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-18). Common (popmax 33.2%, eas) — too common for a highly-penetrant pathogenic allele; Associated with NCOR2-related disorder.

What condition is associated with NCOR2 p.Arg1653= (c.4959A>G)?

NCOR2 p.Arg1653= (c.4959A>G) is associated with NCOR2-related disorder (ClinVar).

NCOR2 p.Arg1653=

Q: How common is NCOR2 p.Arg1653= (c.4959A>G) in the general population?

NCOR2 p.Arg1653= (c.4959A>G) is common (popmax 33.2%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4959A>G · rs2230942 · VCV3059345

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 33.2%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

NCOR2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.033	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.034	GERP -4.1, phastCons 0.75
Overall
CADD	7.953	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 33.2% East Asian · 14,863/44,778 alleles

Filtering AF 32.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 32.6%

Overall 8.64% 139,144/1,610,632 alleles · common exomes 117,807/1,458,542 · genomes 21,337/152,090 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	33.2%	3
African / African-American	28.1%	4
Finnishnot grpmax-eligible	13.9%	7
Remaining individualsnot grpmax-eligible	10.1%	10
Admixed American	8.6%	12
European (non-Finnish)	6.63%	15
Middle Eastern	5.77%	17
South Asian	3.88%	26
Ashkenazi Jewishnot grpmax-eligible	3.86%	26
Amishnot grpmax-eligible	0.658%	152

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.Arg1653=
Coding: c.4959A>G
MANE Select: NM_006312
dbSNP: rs2230942
Type: single nucleotide variant
Location: chr12:124342052 (GRCh38)
Gene constraint: LOEUF 0.448 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 41.00 · 36 PDB
Residue 1653: a modified residue (asymmetric dimethylarginine)

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

Disease context

NCOR2-related disorder

Similar variants

NCOR2 p.Arg1653Gln Uncertain significance ★ ⚠ same residue
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

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-arg1653 (accessed [today's date]).

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