Is NCOR2 p.Pro1028Ser (c.3082C>T) pathogenic?

NCOR2 p.Pro1028Ser (c.3082C>T) is classified Uncertain significance in NCOR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-23). AlphaMissense: likely benign (0.0886); Very rare (popmax 0.00314%, sas).

How common is NCOR2 p.Pro1028Ser (c.3082C>T) in the general population?

NCOR2 p.Pro1028Ser (c.3082C>T) is very rare (popmax 0.00314%, sas) (gnomAD).

What do computational predictors say about NCOR2 p.Pro1028Ser (c.3082C>T)?

AlphaMissense predicts likely benign (score 0.0886) — an in-silico prediction, not a clinical call.

NCOR2 p.Pro1028Ser

c.3082C>T · rs2547498493 · VCV2478275

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0886 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00314%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0886	likely benign
REVEL	0.071	moderately benign-leaning
SaProt	LLR -6.84	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 8.5	GERP 1.6, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 34 kb · p 0.77 · regional, not allelic
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00314% South Asian · 1/31,838 alleles

Overall 0.000261% 3/1,150,382 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00314%	31,838
Remaining individualsnot grpmax-eligible	0.00206%	48,442
European (non-Finnish)	9.75e-05%	1,025,678

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.Pro1028Ser
Coding: c.3082C>T
MANE Select: NM_006312
dbSNP: rs2547498493
Type: single nucleotide variant
Location: chr12:124362144 (GRCh38)
Gene constraint: LOEUF 0.448 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 41.00 · 36 PDB
Residue 1028: the 'disordered' region

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

Similar variants

NCOR2 p.Ala1526Thr Uncertain significance ★★ ⚠ same type
NCOR2 p.Arg2174Cys Uncertain significance ★★ ⚠ same type
NCOR2 p.Arg2467Gln Uncertain significance ★★ ⚠ same type
NCOR2 p.Gly1520Ser Uncertain significance ★★ ⚠ same type
NCOR2 c.3986-17C>T Benign ★★ same type
NCOR2 c.6265+16T>C Benign ★★ same type
NCOR2 c.-36G>C Benign ★★ same type
NCOR2 p.Ala1699Thr Benign ★★ same type

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-pro1028ser (accessed [today's date]).

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