Is BCOR p.Thr1365= (c.4095C>G) pathogenic?

BCOR p.Thr1365= (c.4095C>G) is classified Likely benign in BCOR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-25). Ultra-rare (popmax 0.023%, mid); Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Thr1365= (c.4095C>G)?

BCOR p.Thr1365= (c.4095C>G) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Thr1365= (c.4095C>G) in the general population?

BCOR p.Thr1365= (c.4095C>G) is ultra-rare (popmax 0.023%, mid) (gnomAD).

BCOR p.Thr1365=

c.4095C>G · rs750841214 · VCV2757264

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.023%, mid)

Conditions

microphthalmia, syndromic 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.142	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.7, phastCons 1
Overall
CADD	6.572	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.023% Middle Eastern · 1/4,356 alleles

Filtering AF 0.00459% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00124% 15/1,210,197 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.023%	4,356
South Asian	0.0106%	9,458
Admixed American	0.00218%	45,863
Remaining individualsnot grpmax-eligible	0.0021%	47,616
European (non-Finnish)	0.00067%	149,192

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.Thr1365=
Coding: c.4095C>G
MANE Select: NM_001123385
dbSNP: rs750841214
Type: single nucleotide variant
Location: chrX:40062824 (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.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-thr1365 (accessed [today's date]).

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