Is BCOR p.Thr1730= (c.5190G>A) pathogenic?

BCOR p.Thr1730= (c.5190G>A) is classified Benign/Likely benign in BCOR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-01). Ultra-rare (popmax 0.0914%, mid); Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Thr1730= (c.5190G>A)?

BCOR p.Thr1730= (c.5190G>A) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Thr1730= (c.5190G>A) in the general population?

BCOR p.Thr1730= (c.5190G>A) is ultra-rare (popmax 0.0914%, mid) (gnomAD).

BCOR p.Thr1730=

c.5190G>A · rs375139386 · VCV696103

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0914%, mid)

Conditions

microphthalmia, syndromic 2

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 -3.1	GERP -3.1
Overall
CADD	0.035	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0914% Middle Eastern · 4/4,374 alleles

Filtering AF 0.0362% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0314%

Overall 0.0226% 273/1,209,128 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0914%	1,093
African / African-American	0.0507%	1,974
Ashkenazi Jewishnot grpmax-eligible	0.0318%	3,145
European (non-Finnish)	0.0244%	4,104
Remaining individualsnot grpmax-eligible	0.0189%	5,285
East Asian	0.00592%	16,890
South Asian	0.00354%	28,274
Admixed American	0.00219%	45,661
Finnishnot grpmax-eligible	0.00215%	46,523

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.Thr1730=
Coding: c.5190G>A
MANE Select: NM_001123385
dbSNP: rs375139386
Type: single nucleotide variant
Location: chrX:40052187 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 1730: the 'necessary and sufficient for interaction with pcgf1' 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

BCOR p.Thr1730Met 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-thr1730 (accessed [today's date]).

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