Is BCOR p.Pro326= (c.978G>A) pathogenic?

BCOR p.Pro326= (c.978G>A) is classified Likely benign in BCOR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-23). Rare (popmax 0.139%, amr); Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Pro326= (c.978G>A)?

BCOR p.Pro326= (c.978G>A) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Pro326= (c.978G>A) in the general population?

BCOR p.Pro326= (c.978G>A) is rare (popmax 0.139%, amr) (gnomAD).

BCOR p.Pro326=

c.978G>A · rs751650335 · VCV257506

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.139%, 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 -13	GERP -3.2
Overall
CADD	0.052	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.139% Admixed American · 64/45,894 alleles

Filtering AF 0.112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.102%

Overall 0.0086% 104/1,209,727 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.139%	717
Remaining individualsnot grpmax-eligible	0.0336%	2,974
African / African-American	0.0122%	8,215
European (non-Finnish)	0.00179%	55,931
South Asian	0.00176%	56,662

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.Pro326=
Coding: c.978G>A
MANE Select: NM_001123385
dbSNP: rs751650335
Type: single nucleotide variant
Location: chrX:40074368 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 326: 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.Pro326Leu Uncertain significance ★★ same residue
BCOR p.Pro326Ala 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

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-pro326 (accessed [today's date]).

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