Is BCOR p.Phe713Leu (c.2139T>A) pathogenic?

BCOR p.Phe713Leu (c.2139T>A) is classified Uncertain significance in BCOR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-08). AlphaMissense: likely pathogenic (0.9967); Very rare (popmax 0.00433%, amr); Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Phe713Leu (c.2139T>A)?

BCOR p.Phe713Leu (c.2139T>A) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Phe713Leu (c.2139T>A) in the general population?

BCOR p.Phe713Leu (c.2139T>A) is very rare (popmax 0.00433%, amr) (gnomAD).

What do computational predictors say about BCOR p.Phe713Leu (c.2139T>A)?

AlphaMissense predicts likely pathogenic (score 0.9967) — an in-silico prediction, not a clinical call.

BCOR p.Phe713Leu

c.2139T>A · VCV4740556

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9967 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00433%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microphthalmia, syndromic 2

Computational evidence

Protein change
AlphaMissense	0.9967	likely pathogenic · top 4% in BCOR
REVEL	0.271	benign-leaning
SaProt	LLR -5.24	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.03	GERP -0.58, phastCons 0.03
Regional constraint	o/e 0.90	unconstrained · MANE · 2,116 bp · p 0.013 · regional, not allelic
Overall
CADD	20.6	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

Grpmax group 0.00433% Admixed American · 2/46,150 alleles

Filtering AF 0.000718% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000269%

Overall 0.000182% 2/1,098,241 alleles · very rare

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.Phe713Leu
Coding: c.2139T>A
MANE Select: NM_001123385
Type: single nucleotide variant
Location: chrX:40073207 (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

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BCOR p.Arg976Ter Pathogenic ★★ same condition
BCOR p.Ala1262Ser Uncertain significance ★★ ⚠ same condition
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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-phe713leu (accessed [today's date]).

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