Is NCOR2 p.Pro154= (c.462G>A) pathogenic?

NCOR2 p.Pro154= (c.462G>A) is classified Benign in NCOR2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2020-04-20). Common (popmax 19.1%, sas) — too common for a highly-penetrant pathogenic allele.

NCOR2 p.Pro154=

Q: How common is NCOR2 p.Pro154= (c.462G>A) in the general population?

NCOR2 p.Pro154= (c.462G>A) is common (popmax 19.1%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.462G>A · rs10846679 · VCV1286492

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 19.1%, sas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.012	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -17
Overall
CADD	0.047	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 19.1% South Asian · 17,371/91,054 alleles

Filtering AF 18.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 18.7%

Overall 12.9% 207,752/1,613,712 alleles · common exomes 192,571/1,461,626 · genomes 15,181/152,086 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	19.1%	5
East Asian	16.8%	6
Admixed American	15.5%	6
European (non-Finnish)	12.9%	8
Remaining individualsnot grpmax-eligible	12.8%	8
Ashkenazi Jewishnot grpmax-eligible	11.9%	8
Finnishnot grpmax-eligible	11.9%	8
Middle Eastern	9.23%	11
Amishnot grpmax-eligible	4.62%	22
African / African-American	2.6%	38

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.Pro154=
Coding: c.462G>A
MANE Select: NM_006312
dbSNP: rs10846679
Type: single nucleotide variant
Location: chr12:124473081 (GRCh38)
Gene constraint: LOEUF 0.448 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 41.00 · 36 PDB
Residue 154: the 'disordered' region

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

Similar variants

NCOR2 p.Pro154Leu Uncertain significance ★ ⚠ same residue
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

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-pro154 (accessed [today's date]).

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