Is NCOR2 p.Pro1204= (c.3612G>A) pathogenic?

NCOR2 p.Pro1204= (c.3612G>A) is classified Benign in NCOR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-26). Low-frequency (popmax 4.87%, eas); Associated with NCOR2-related disorder.

What condition is associated with NCOR2 p.Pro1204= (c.3612G>A)?

NCOR2 p.Pro1204= (c.3612G>A) is associated with NCOR2-related disorder (ClinVar).

How common is NCOR2 p.Pro1204= (c.3612G>A) in the general population?

NCOR2 p.Pro1204= (c.3612G>A) is low-frequency (popmax 4.87%, eas) (gnomAD).

NCOR2 p.Pro1204=

c.3612G>A · rs2271143 · VCV3044955

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 4.87%, eas)

Conditions

NCOR2-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 -14	GERP -3.2
Overall
CADD	0.306	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.87% East Asian · 2,170/44,584 alleles

Filtering AF 4.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.63%

Overall 0.163% 2,621/1,604,882 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	4.87%	21
Remaining individualsnot grpmax-eligible	0.291%	344
Ashkenazi Jewishnot grpmax-eligible	0.224%	447
South Asian	0.13%	769
Middle Eastern	0.033%	3,028
Admixed American	0.0269%	3,717
African / African-American	0.02%	4,994
European (non-Finnish)	0.00458%	21,810

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.Pro1204=
Coding: c.3612G>A
MANE Select: NM_006312
dbSNP: rs2271143
Type: single nucleotide variant
Location: chr12:124354174 (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

Disease context

NCOR2-related disorder

Similar variants

NCOR2 p.Pro1204Ala Uncertain significance ★ ⚠ same residue
NCOR2 p.Pro1204Thr Uncertain significance ★ ⚠ same residue
NCOR2 p.Ala1526Thr Uncertain significance ★★ ⚠ same condition
NCOR2 p.Arg2467Gln Uncertain significance ★★ ⚠ same condition
NCOR2 c.1329-4G>A Benign same condition
NCOR2 c.3242-9G>A Benign same condition
NCOR2 c.6411+8C>T Likely benign same condition
NCOR2 c.7364-5C>T Likely benign 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/ncor2-p-pro1204 (accessed [today's date]).

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