Is BCOR p.Pro1648Arg (c.4943C>G) pathogenic?

BCOR p.Pro1648Arg (c.4943C>G) is classified Uncertain significance in BCOR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-01). AlphaMissense: likely pathogenic (0.9159); Absent from gnomAD v4.1.

How common is BCOR p.Pro1648Arg (c.4943C>G) in the general population?

BCOR p.Pro1648Arg (c.4943C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BCOR p.Pro1648Arg (c.4943C>G)?

AlphaMissense predicts likely pathogenic (score 0.9159) — an in-silico prediction, not a clinical call.

BCOR p.Pro1648Arg

c.4943C>G · rs763651353 · VCV2660305

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9159 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9159	likely pathogenic
REVEL	0.576	indeterminate
SaProt	LLR -4.62	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 3,308 bp · p 0.29 · regional, not allelic
Overall
CADD	24.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BCOR
Protein: p.Pro1648Arg
Coding: c.4943C>G
MANE Select: NM_001123385
dbSNP: rs763651353
Type: single nucleotide variant
Location: chrX:40053919 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 1648: 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.Pro1648= Likely benign ★★ same residue
BCOR p.Pro1648Leu Conflicting classifications of pathogenicity ★ ⚠ 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

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-pro1648arg (accessed [today's date]).

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