Is NCOR1 p.Pro225= (c.675T>A) pathogenic?

NCOR1 p.Pro225= (c.675T>A) is classified Benign in NCOR1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-21). Common (popmax 5.19%, eas) — too common for a highly-penetrant pathogenic allele; Associated with NCOR1-related disorder.

What condition is associated with NCOR1 p.Pro225= (c.675T>A)?

NCOR1 p.Pro225= (c.675T>A) is associated with NCOR1-related disorder (ClinVar).

NCOR1 p.Pro225=

Q: How common is NCOR1 p.Pro225= (c.675T>A) in the general population?

NCOR1 p.Pro225= (c.675T>A) is common (popmax 5.19%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.675T>A · rs74841437 · VCV3052795

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 5.19%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

NCOR1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.8	GERP -3.1, phastCons 0.97
Overall
CADD	9.015	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.19% East Asian · 2,329/44,876 alleles

Filtering AF 5.01% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.94%

Overall 0.173% 2,790/1,614,126 alleles · common exomes 2,364/1,461,856 · genomes 426/152,270 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	5.19%	19
Remaining individualsnot grpmax-eligible	0.358%	279
South Asian	0.142%	706
African / African-American	0.06%	1,667
Admixed American	0.0367%	2,728
European (non-Finnish)	0.00347%	28,781

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: NCOR1
Protein: p.Pro225=
Coding: c.675T>A
MANE Select: NM_006311
dbSNP: rs74841437
Type: single nucleotide variant
Location: chr17:16158817 (GRCh38)
Gene constraint: LOEUF 0.292 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 41.40 · 27 PDB
Residue 225: the 'interaction with zbtb33 and hexim1' region; the 'disordered' region

Full NCOR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

NCOR1-related disorder

Similar variants

NCOR1 p.Arg1561Trp Uncertain significance ★ same condition
NCOR1 p.Arg1876Thr Uncertain significance ★ ⚠ same condition
NCOR1 p.Asp1944Val Uncertain significance ★ ⚠ same condition
NCOR1 p.Thr2243Met Uncertain significance ★ ⚠ same condition
NCOR1 p.Arg33Cys Likely pathogenic ⚠ same condition
NCOR1 p.Gly1634Arg Uncertain significance ⚠ same condition
NCOR1 p.Thr1027Ala Uncertain significance ⚠ same condition
NCOR1 p.Thr1502Ile Uncertain significance ⚠ 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/ncor1-p-pro225 (accessed [today's date]).

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