Is BCOR p.Arg243Cys (c.727C>T) pathogenic?

BCOR p.Arg243Cys (c.727C>T) is classified Uncertain significance in BCOR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-12). AlphaMissense: likely pathogenic (0.8746); Very rare (popmax 0.00217%, amr); Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Arg243Cys (c.727C>T)?

BCOR p.Arg243Cys (c.727C>T) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Arg243Cys (c.727C>T) in the general population?

BCOR p.Arg243Cys (c.727C>T) is very rare (popmax 0.00217%, amr) (gnomAD).

What do computational predictors say about BCOR p.Arg243Cys (c.727C>T)?

AlphaMissense predicts likely pathogenic (score 0.8746) — an in-silico prediction, not a clinical call.

BCOR p.Arg243Cys

c.727C>T · VCV3480288

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8746 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00217%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microphthalmia, syndromic 2

Computational evidence

Protein change
AlphaMissense	0.8746	likely pathogenic
REVEL	0.709	pathogenic-leaning
SaProt	LLR -8.14	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.26	constrained · MANE · 87 bp · p 0.00032 · regional, not allelic
Overall
CADD	28.6	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 0.00217% Admixed American · 1/46,112 alleles

Overall 9.11e-05% 1/1,098,045 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.Arg243Cys
Coding: c.727C>T
MANE Select: NM_001123385
Type: single nucleotide variant
Location: chrX:40074619 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB

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

Disease context

microphthalmia, syndromic 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BCOR p.Arg243His Uncertain significance ★★ ⚠ same residue
BCOR p.Arg1163Ter Pathogenic ★★ same condition
BCOR p.Arg1217Ter Pathogenic ★★ same condition
BCOR p.Arg1514Ter Pathogenic ★★ same condition
BCOR p.Arg342Ter Pathogenic ★★ same condition
BCOR p.Arg976Ter Pathogenic ★★ same condition
BCOR p.Ala1262Ser Uncertain significance ★★ ⚠ same condition
BCOR p.Ala1307Pro 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-arg243cys (accessed [today's date]).

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