Is NCOR2 p.Ala241= (c.723A>C) pathogenic?

NCOR2 p.Ala241= (c.723A>C) is classified Likely benign in NCOR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-15). Very rare (popmax 0.00174%, nfe); Associated with NCOR2-related disorder.

What condition is associated with NCOR2 p.Ala241= (c.723A>C)?

NCOR2 p.Ala241= (c.723A>C) is associated with NCOR2-related disorder (ClinVar).

How common is NCOR2 p.Ala241= (c.723A>C) in the general population?

NCOR2 p.Ala241= (c.723A>C) is very rare (popmax 0.00174%, nfe) (gnomAD).

NCOR2 p.Ala241=

c.723A>C · rs992462302 · VCV3053222

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00174%, nfe)

Conditions

NCOR2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.068	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.3	GERP -3.3
Overall
CADD	0.898	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00174% European (non-Finnish) · 20/1,151,182 alleles

Filtering AF 0.00113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000922%

Overall 0.00137% 21/1,532,154 alleles · very rare exomes 19/1,380,580 · genomes 2/151,574 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00174%	57,559
Remaining individualsnot grpmax-eligible	0.0017%	58,910

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.Ala241=
Coding: c.723A>C
MANE Select: NM_006312
dbSNP: rs992462302
Type: single nucleotide variant
Location: chr12:124457145 (GRCh38)
Gene constraint: LOEUF 0.448 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 41.00 · 36 PDB

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-ala241 (accessed [today's date]).

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