Is NCOR2 p.Arg178= (c.534C>T) pathogenic?

NCOR2 p.Arg178= (c.534C>T) is classified Likely benign in NCOR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-14). Very rare (popmax 0.00801%, afr).

How common is NCOR2 p.Arg178= (c.534C>T) in the general population?

NCOR2 p.Arg178= (c.534C>T) is very rare (popmax 0.00801%, afr) (gnomAD).

NCOR2 p.Arg178=

c.534C>T · VCV4556550

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.305	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -14
Overall
CADD	0.615	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,912 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.00273% 44/1,614,018 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,485
Remaining individualsnot grpmax-eligible	0.0048%	20,829
East Asian	0.00445%	22,449
European (non-Finnish)	0.00263%	38,066
Admixed American	0.00167%	60,000
South Asian	0.0011%	91,082

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.Arg178=
Coding: c.534C>T
MANE Select: NM_006312
Type: single nucleotide variant
Location: chr12:124473009 (GRCh38)
Gene constraint: LOEUF 0.448 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 41.00 · 36 PDB
Residue 178: an α-helix

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-arg178 (accessed [today's date]).

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