Is NCOR1 p.Pro1692= (c.5076G>A) pathogenic?

NCOR1 p.Pro1692= (c.5076G>A) is classified Likely benign in NCOR1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-28). Ultra-rare (popmax 0.0826%, sas); Associated with NCOR1-related disorder.

What condition is associated with NCOR1 p.Pro1692= (c.5076G>A)?

NCOR1 p.Pro1692= (c.5076G>A) is associated with NCOR1-related disorder (ClinVar).

How common is NCOR1 p.Pro1692= (c.5076G>A) in the general population?

NCOR1 p.Pro1692= (c.5076G>A) is ultra-rare (popmax 0.0826%, sas) (gnomAD).

NCOR1 p.Pro1692=

c.5076G>A · rs377698372 · VCV3038963

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0826%, sas)

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 -10	GERP -3.6
Overall
CADD	0.864	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0826% South Asian · 75/90,818 alleles

Filtering AF 0.0675% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0619%

Overall 0.0326% 525/1,611,790 alleles · ultra-rare exomes 499/1,459,666 · genomes 26/152,124 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0826%	1,211
European (non-Finnish)	0.0357%	2,800
Remaining individualsnot grpmax-eligible	0.0337%	2,971
Middle Eastern	0.0329%	3,038
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,510
Admixed American	0.00334%	29,920
Finnishnot grpmax-eligible	0.00313%	31,991
East Asian	0.00223%	44,830

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.Pro1692=
Coding: c.5076G>A
MANE Select: NM_006311
dbSNP: rs377698372
Type: single nucleotide variant
Location: chr17:16064895 (GRCh38)
Gene constraint: LOEUF 0.292 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 41.40 · 27 PDB
Residue 1692: the 'interaction with c1d' region; the 'disordered' region; the 'interaction with eto' 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-pro1692 (accessed [today's date]).

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