Is BCOR p.Pro339= (c.1017G>A) pathogenic?

BCOR p.Pro339= (c.1017G>A) is classified Likely benign in BCOR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). Ultra-rare (popmax 0.0283%, amr); Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Pro339= (c.1017G>A)?

BCOR p.Pro339= (c.1017G>A) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Pro339= (c.1017G>A) in the general population?

BCOR p.Pro339= (c.1017G>A) is ultra-rare (popmax 0.0283%, amr) (gnomAD).

BCOR p.Pro339=

c.1017G>A · VCV4802027

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0283%, amr)

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 0.21	GERP -3.2, phastCons 0.61
Overall
CADD	4.464	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0283% Admixed American · 13/45,935 alleles

Filtering AF 0.0167% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0132%

Overall 0.00248% 30/1,210,337 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0283%	3,533
East Asian	0.00888%	11,258
Remaining individualsnot grpmax-eligible	0.0063%	15,861
European (non-Finnish)	0.00123%	81,389

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.Pro339=
Coding: c.1017G>A
MANE Select: NM_001123385
Type: single nucleotide variant
Location: chrX:40074329 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 339: 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

BCOR p.Pro339Leu 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-pro339 (accessed [today's date]).

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