Is BCOR p.Arg1678His (c.5033G>A) pathogenic?

BCOR p.Arg1678His (c.5033G>A) is classified Likely benign in BCOR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: ambiguous (0.4722); Very rare (popmax 0.00176%, sas).

How common is BCOR p.Arg1678His (c.5033G>A) in the general population?

BCOR p.Arg1678His (c.5033G>A) is very rare (popmax 0.00176%, sas) (gnomAD).

What do computational predictors say about BCOR p.Arg1678His (c.5033G>A)?

AlphaMissense predicts ambiguous (score 0.4722) — an in-silico prediction, not a clinical call.

BCOR p.Arg1678His

c.5033G>A · VCV4280975

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4722 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00176%, sas)

Computational evidence

Protein change
AlphaMissense	0.4722	ambiguous
REVEL	0.434	indeterminate
SaProt	LLR -5.76	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 3,308 bp · p 0.29 · regional, not allelic
Overall
CADD	24.0	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 0.00176% South Asian · 1/56,832 alleles

Filtering AF 0.000565% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000412%

Overall 0.000992% 12/1,209,621 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00176%	56,832
African / African-American	0.00175%	57,185
European (non-Finnish)	0.00112%	89,485

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.Arg1678His
Coding: c.5033G>A
MANE Select: NM_001123385
Type: single nucleotide variant
Location: chrX:40052344 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 1678: the 'necessary and sufficient for interaction with pcgf1' region; an α-helix

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

Similar variants

BCOR p.Arg1678Gly Uncertain significance ★ ⚠ same residue
BCOR p.Arg1163Ter Pathogenic ★★ same type
BCOR p.Arg1164Ter Pathogenic ★★ same type
BCOR p.Arg1217Ter Pathogenic ★★ same type
BCOR p.Arg1514Ter Pathogenic ★★ same type
BCOR p.Arg342Ter Pathogenic ★★ same type
BCOR p.Arg810Ter Pathogenic ★★ same type
BCOR p.Arg976Ter Pathogenic ★★ 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/bcor-p-arg1678his (accessed [today's date]).

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