Is BCOR p.Ser593= (c.1779C>A) pathogenic?

BCOR p.Ser593= (c.1779C>A) is classified Benign in BCOR (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-23). Low-frequency (popmax 4.99%, afr); Associated with History of neurodevelopmental disorder.

What condition is associated with BCOR p.Ser593= (c.1779C>A)?

BCOR p.Ser593= (c.1779C>A) is associated with History of neurodevelopmental disorder, microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Ser593= (c.1779C>A) in the general population?

BCOR p.Ser593= (c.1779C>A) is low-frequency (popmax 4.99%, afr) (gnomAD).

BCOR p.Ser593=

c.1779C>A · rs17145652 · VCV128523

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.99%, afr)

Conditions

History of neurodevelopmental disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.4	GERP -3.5
Overall
CADD	0.233	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.99% African / African-American · 2,876/57,593 alleles

Filtering AF 4.84% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.78%

Overall 0.305% 3,696/1,211,089 alleles · low-frequency exomes 2,084/1,097,970 · genomes 1,612/113,119 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.99%	20
Ashkenazi Jewishnot grpmax-eligible	1.35%	74
Remaining individualsnot grpmax-eligible	0.453%	221
Admixed American	0.369%	271
Middle Eastern	0.299%	335
European (non-Finnish)	0.0132%	7,589
South Asian	0.0105%	9,487

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.Ser593=
Coding: c.1779C>A
MANE Select: NM_001123385
dbSNP: rs17145652
Type: single nucleotide variant
Location: chrX:40073567 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 593: the 'disordered' region

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

Disease context

History of neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: microphthalmia, syndromic 2

Similar variants

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
BCOR p.Ala165Pro 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-ser593 (accessed [today's date]).

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