Is BCOR p.Lys429= (c.1287G>A) pathogenic?

BCOR p.Lys429= (c.1287G>A) is classified Likely benign in BCOR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-08). Very rare (popmax 0.00491%, nfe); Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Lys429= (c.1287G>A)?

BCOR p.Lys429= (c.1287G>A) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Lys429= (c.1287G>A) in the general population?

BCOR p.Lys429= (c.1287G>A) is very rare (popmax 0.00491%, nfe) (gnomAD).

BCOR p.Lys429=

c.1287G>A · rs775664343 · VCV695642

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00491%, nfe)

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 2.2	GERP 1.6, phastCons 1
Overall
CADD	8.389	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00491% European (non-Finnish) · 44/895,428 alleles

Filtering AF 0.00372% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00332%

Overall 0.00396% 48/1,210,923 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0084%	11,905
European (non-Finnish)grpmax	0.00491%	20,351

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys429=
Coding: c.1287G>A
MANE Select: NM_001123385
dbSNP: rs775664343
Type: single nucleotide variant
Location: chrX:40074059 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 429: 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.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-lys429 (accessed [today's date]).

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