Is BCOR p.Pro1427= (c.4281A>T) pathogenic?

BCOR p.Pro1427= (c.4281A>T) is classified Benign in BCOR (ClinVar, Single submitter, 2 submitters; last evaluated 2023-07-19). Ultra-rare (popmax 0.0403%, afr); Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Pro1427= (c.4281A>T)?

BCOR p.Pro1427= (c.4281A>T) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Pro1427= (c.4281A>T) in the general population?

BCOR p.Pro1427= (c.4281A>T) is ultra-rare (popmax 0.0403%, afr) (gnomAD).

BCOR p.Pro1427=

c.4281A>T · rs148520586 · VCV2098973

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0403%, afr)

Conditions

microphthalmia, syndromic 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.021	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.8	GERP -3.1
Overall
CADD	0.162	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0403% African / African-American · 23/57,038 alleles

Filtering AF 0.0275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0233%

Overall 0.00199% 24/1,208,540 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0403%	2,480
Admixed American	0.00219%	45,640

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.Pro1427=
Coding: c.4281A>T
MANE Select: NM_001123385
dbSNP: rs148520586
Type: single nucleotide variant
Location: chrX:40062286 (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-pro1427 (accessed [today's date]).

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