Is BCOR p.Arg566Cys (c.1696C>T) pathogenic?

BCOR p.Arg566Cys (c.1696C>T) is classified Uncertain significance in BCOR (ClinVar, Single submitter, 1 submitter; last evaluated 2019-03-08). AlphaMissense: ambiguous (0.5388); Very rare (popmax 0.00172%, afr); Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Arg566Cys (c.1696C>T)?

BCOR p.Arg566Cys (c.1696C>T) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Arg566Cys (c.1696C>T) in the general population?

BCOR p.Arg566Cys (c.1696C>T) is very rare (popmax 0.00172%, afr) (gnomAD).

What do computational predictors say about BCOR p.Arg566Cys (c.1696C>T)?

AlphaMissense predicts ambiguous (score 0.5388) — an in-silico prediction, not a clinical call.

BCOR p.Arg566Cys

c.1696C>T · rs1935607481 · VCV976295

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5388 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00172%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

microphthalmia, syndromic 2

Computational evidence

Protein change
AlphaMissense	0.5388	ambiguous
REVEL	0.242	benign-leaning
SaProt	LLR -8.23	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 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 2,116 bp · p 0.013 · 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 0.00172% African / African-American · 1/57,991 alleles

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

Overall 0.000546% 6/1,098,150 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00172%	57,991
European (non-Finnish)	0.000558%	179,137

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.Arg566Cys
Coding: c.1696C>T
MANE Select: NM_001123385
dbSNP: rs1935607481
Type: single nucleotide variant
Location: chrX:40073650 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 566: the 'disordered' region

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

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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-arg566cys (accessed [today's date]).

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