Is BCOR p.Asp1352Asn (c.4054G>A) pathogenic?

BCOR p.Asp1352Asn (c.4054G>A) is classified Uncertain significance in BCOR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.0842); Ultra-rare (popmax 0.0229%, mid); Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Asp1352Asn (c.4054G>A)?

BCOR p.Asp1352Asn (c.4054G>A) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Asp1352Asn (c.4054G>A) in the general population?

BCOR p.Asp1352Asn (c.4054G>A) is ultra-rare (popmax 0.0229%, mid) (gnomAD).

What do computational predictors say about BCOR p.Asp1352Asn (c.4054G>A)?

AlphaMissense predicts likely benign (score 0.0842) — an in-silico prediction, not a clinical call.

BCOR p.Asp1352Asn

c.4054G>A · VCV3697432

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0842 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0229%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microphthalmia, syndromic 2

Computational evidence

Protein change
AlphaMissense	0.0842	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -6.44	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 1.6, phastCons 0.99
Regional constraint	o/e 1.07	unconstrained · MANE · 2,355 bp · p 0.26 · regional, not allelic
Overall
CADD	20.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0229% Middle Eastern · 1/4,375 alleles

Filtering AF 0.00146% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00119%

Overall 0.00215% 26/1,209,868 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0229%	4,375
South Asian	0.00529%	18,893
Admixed American	0.00436%	22,920
European (non-Finnish)	0.00223%	44,748

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.Asp1352Asn
Coding: c.4054G>A
MANE Select: NM_001123385
Type: single nucleotide variant
Location: chrX:40062865 (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
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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-asp1352asn (accessed [today's date]).

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