Is NCOR2 p.His44Pro (c.131A>C) pathogenic?

NCOR2 p.His44Pro (c.131A>C) is classified Uncertain significance in NCOR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.0723); Very rare (popmax 0.0023%, eas).

How common is NCOR2 p.His44Pro (c.131A>C) in the general population?

NCOR2 p.His44Pro (c.131A>C) is very rare (popmax 0.0023%, eas) (gnomAD).

What do computational predictors say about NCOR2 p.His44Pro (c.131A>C)?

AlphaMissense predicts likely benign (score 0.0723) — an in-silico prediction, not a clinical call.

NCOR2 p.His44Pro

c.131A>C · VCV4118035

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0723 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0023%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0723	likely benign
REVEL	0.232	benign-leaning
SaProt	LLR -5.56	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.3	GERP 5.9, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 22 kb · p 0.61 · regional, not allelic
Overall
CADD	20.2	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 0.0023% East Asian · 1/43,516 alleles

Overall 6.29e-05% 1/1,589,664 alleles · very rare exomes 1/1,437,414 · genomes 0/152,250 · joint denominator

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.His44Pro
Coding: c.131A>C
MANE Select: NM_006312
Type: single nucleotide variant
Location: chr12:124486543 (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

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-his44pro (accessed [today's date]).

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