Is BCOR p.Glu242Lys (c.724G>A) pathogenic?

BCOR p.Glu242Lys (c.724G>A) is classified Uncertain significance in BCOR (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-27). AlphaMissense: likely pathogenic (0.9646); Absent from gnomAD v4.1; Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Glu242Lys (c.724G>A)?

BCOR p.Glu242Lys (c.724G>A) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Glu242Lys (c.724G>A) in the general population?

BCOR p.Glu242Lys (c.724G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BCOR p.Glu242Lys (c.724G>A)?

AlphaMissense predicts likely pathogenic (score 0.9646) — an in-silico prediction, not a clinical call.

BCOR p.Glu242Lys

c.724G>A · rs1935694930 · VCV858993

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9646 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

microphthalmia, syndromic 2

Computational evidence

Protein change
AlphaMissense	0.9646	likely pathogenic · top 10% in BCOR
REVEL	0.436	indeterminate
SaProt	LLR -7.58	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.26	constrained · MANE · 87 bp · p 0.00032 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BCOR
Protein: p.Glu242Lys
Coding: c.724G>A
MANE Select: NM_001123385
dbSNP: rs1935694930
Type: single nucleotide variant
Location: chrX:40074622 (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-glu242lys (accessed [today's date]).

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