Is BCOR p.Arg1589Cys (c.4765C>T) pathogenic?

BCOR p.Arg1589Cys (c.4765C>T) is classified Benign/Likely benign in BCOR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-03-18). AlphaMissense: likely benign (0.1471); Rare (popmax 0.429%, sas); Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Arg1589Cys (c.4765C>T)?

BCOR p.Arg1589Cys (c.4765C>T) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Arg1589Cys (c.4765C>T) in the general population?

BCOR p.Arg1589Cys (c.4765C>T) is rare (popmax 0.429%, sas) (gnomAD).

What do computational predictors say about BCOR p.Arg1589Cys (c.4765C>T)?

AlphaMissense predicts likely benign (score 0.1471) — an in-silico prediction, not a clinical call.

BCOR p.Arg1589Cys

c.4765C>T · rs754643148 · VCV1276010

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1471 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.429%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

microphthalmia, syndromic 2

Computational evidence

Protein change
AlphaMissense	0.1471	likely benign
REVEL	0.384	indeterminate
SaProt	LLR -7.22	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 0.49, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 3,308 bp · p 0.29 · regional, not allelic
Overall
CADD	24.8	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 0.429% South Asian · 241/56,155 alleles

Filtering AF 0.385% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.367%

Overall 0.0234% 281/1,202,362 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.429%	233
Middle Eastern	0.0462%	2,166
Admixed American	0.0396%	2,528
Remaining individualsnot grpmax-eligible	0.019%	5,265
African / African-American	0.0105%	9,484
European (non-Finnish)	0.000562%	177,873

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.Arg1589Cys
Coding: c.4765C>T
MANE Select: NM_001123385
dbSNP: rs754643148
Type: single nucleotide variant
Location: chrX:40054310 (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.Arg1589His 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-arg1589cys (accessed [today's date]).

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