Is BCOR p.Asp1389His (c.4165G>C) pathogenic?

BCOR p.Asp1389His (c.4165G>C) is classified Uncertain significance in BCOR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-22). AlphaMissense: ambiguous (0.4977); Very rare (popmax 0.000559%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BCOR p.Asp1389His (c.4165G>C)?

BCOR p.Asp1389His (c.4165G>C) is associated with Inborn genetic diseases (ClinVar).

How common is BCOR p.Asp1389His (c.4165G>C) in the general population?

BCOR p.Asp1389His (c.4165G>C) is very rare (popmax 0.000559%, nfe) (gnomAD).

What do computational predictors say about BCOR p.Asp1389His (c.4165G>C)?

AlphaMissense predicts ambiguous (score 0.4977) — an in-silico prediction, not a clinical call.

BCOR p.Asp1389His

c.4165G>C · VCV4595975

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4977 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000559%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4977	ambiguous
REVEL	0.198	benign-leaning
SaProt	LLR -7.85	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.7, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 2,355 bp · p 0.26 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000559% European (non-Finnish) · 5/894,174 alleles

Filtering AF 0.000164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000119%

Overall 0.000456% 5/1,096,574 alleles · very rare

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: BCOR
Protein: p.Asp1389His
Coding: c.4165G>C
MANE Select: NM_001123385
Type: single nucleotide variant
Location: chrX:40062754 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BCOR p.Asp1389Asn Uncertain significance ★ ⚠ same residue
BCOR p.Arg810Ter Pathogenic ★★ same condition
BCOR p.Ala1314Asp Uncertain significance ★★ ⚠ same condition
BCOR p.Ala147Thr Uncertain significance ★★ ⚠ same condition
BCOR p.Ala165Pro Uncertain significance ★★ ⚠ same condition
BCOR p.Arg1231Trp Uncertain significance ★★ ⚠ same condition
BCOR p.Arg763Trp Uncertain significance ★★ ⚠ same condition
BCOR p.Asn193Ser 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/bcor-p-asp1389his (accessed [today's date]).

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