Is NCOR2 p.Pro2001Ser (c.6001C>T) pathogenic?

NCOR2 p.Pro2001Ser (c.6001C>T) is classified Benign in NCOR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-20). AlphaMissense: likely benign (0.079); Common (popmax 12.4%, sas) — too common for a highly-penetrant pathogenic allele; Associated with NCOR2-related disorder.

What condition is associated with NCOR2 p.Pro2001Ser (c.6001C>T)?

NCOR2 p.Pro2001Ser (c.6001C>T) is associated with NCOR2-related disorder (ClinVar).

What do computational predictors say about NCOR2 p.Pro2001Ser (c.6001C>T)?

AlphaMissense predicts likely benign (score 0.079) — an in-silico prediction, not a clinical call.

NCOR2 p.Pro2001Ser

Q: How common is NCOR2 p.Pro2001Ser (c.6001C>T) in the general population?

NCOR2 p.Pro2001Ser (c.6001C>T) is common (popmax 12.4%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.6001C>T · rs2230944 · VCV3056105

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.079 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 12.4%, sas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

NCOR2-related disorder

Computational evidence

Protein change
AlphaMissense	0.079	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -6.21	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.79	GERP -2.6, phastCons 0.19
Regional constraint	o/e 1.05	unconstrained · MANE · 15 kb · p 0.11 · regional, not allelic
Overall
CADD	15.56	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.4% South Asian · 11,274/90,920 alleles

Filtering AF 12.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 12.1%

Overall 4.57% 73,602/1,611,108 alleles · common exomes 66,758/1,458,836 · genomes 6,844/152,272 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	12.4%	8
Amishnot grpmax-eligible	9.1%	11
African / African-American	5.23%	19
Remaining individualsnot grpmax-eligible	4.6%	22
Middle Eastern	4.25%	24
European (non-Finnish)	4.2%	24
East Asian	3.52%	28
Ashkenazi Jewishnot grpmax-eligible	3.18%	31
Admixed American	3%	33
Finnishnot grpmax-eligible	2.16%	46

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.Pro2001Ser
Coding: c.6001C>T
MANE Select: NM_006312
dbSNP: rs2230944
Type: single nucleotide variant
Location: chr12:124336867 (GRCh38)
Gene constraint: LOEUF 0.448 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 41.00 · 36 PDB
Residue 2001: a UniProt-annotated variant site (in); 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-pro2001ser (accessed [today's date]).

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