Is BCOR p.Gln1306Leu (c.3917A>T) pathogenic?

BCOR p.Gln1306Leu (c.3917A>T) is classified Uncertain significance in BCOR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-26). AlphaMissense: likely benign (0.0988); Absent from gnomAD v4.1; Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Gln1306Leu (c.3917A>T)?

BCOR p.Gln1306Leu (c.3917A>T) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Gln1306Leu (c.3917A>T) in the general population?

BCOR p.Gln1306Leu (c.3917A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BCOR p.Gln1306Leu (c.3917A>T)?

AlphaMissense predicts likely benign (score 0.0988) — an in-silico prediction, not a clinical call.

BCOR p.Gln1306Leu

c.3917A>T · rs1215498551 · VCV3024068

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0988 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

microphthalmia, syndromic 2

Computational evidence

Protein change
AlphaMissense	0.0988	likely benign
REVEL	0.334	indeterminate
SaProt	LLR -5.85	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 0.72, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 2,355 bp · p 0.26 · regional, not allelic
Overall
CADD	24.5	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

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.Gln1306Leu
Coding: c.3917A>T
MANE Select: NM_001123385
dbSNP: rs1215498551
Type: single nucleotide variant
Location: chrX:40063002 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 1306: 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.Gln1306fs Pathogenic ★ same residue
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

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-gln1306leu (accessed [today's date]).

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