Is NCOR2 p.Pro1903= (c.5709C>T) pathogenic?

NCOR2 p.Pro1903= (c.5709C>T) is classified Benign in NCOR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-17). Common (popmax 7.48%, afr) — too common for a highly-penetrant pathogenic allele; Associated with NCOR2-related disorder.

What condition is associated with NCOR2 p.Pro1903= (c.5709C>T)?

NCOR2 p.Pro1903= (c.5709C>T) is associated with NCOR2-related disorder (ClinVar).

NCOR2 p.Pro1903=

Q: How common is NCOR2 p.Pro1903= (c.5709C>T) in the general population?

NCOR2 p.Pro1903= (c.5709C>T) is common (popmax 7.48%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.5709C>T · rs3741512 · VCV3043941

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 7.48%, afr) — 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	0.039	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -2.5
Overall
CADD	2.984	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.48% African / African-American · 5,454/72,952 alleles

Filtering AF 7.31% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.24%

Overall 0.436% 6,677/1,530,236 alleles · common exomes 3,465/1,377,940 · genomes 3,212/152,296 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.48%	13
Middle Eastern	0.934%	107
Remaining individualsnot grpmax-eligible	0.721%	139
Admixed American	0.604%	166
East Asian	0.431%	232
South Asian	0.0924%	1,082
European (non-Finnish)	0.0164%	6,102
Ashkenazi Jewishnot grpmax-eligible	0.00374%	26,762
Finnishnot grpmax-eligible	0.00342%	29,266

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.Pro1903=
Coding: c.5709C>T
MANE Select: NM_006312
dbSNP: rs3741512
Type: single nucleotide variant
Location: chr12:124337159 (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-pro1903 (accessed [today's date]).

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