Is BCOR p.Pro1291Leu (c.3872C>T) pathogenic?

BCOR p.Pro1291Leu (c.3872C>T) is classified Uncertain significance in BCOR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-27). AlphaMissense: likely benign (0.0677); Ultra-rare (popmax 0.0184%, afr); Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Pro1291Leu (c.3872C>T)?

BCOR p.Pro1291Leu (c.3872C>T) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Pro1291Leu (c.3872C>T) in the general population?

BCOR p.Pro1291Leu (c.3872C>T) is ultra-rare (popmax 0.0184%, afr) (gnomAD).

What do computational predictors say about BCOR p.Pro1291Leu (c.3872C>T)?

AlphaMissense predicts likely benign (score 0.0677) — an in-silico prediction, not a clinical call.

BCOR p.Pro1291Leu

c.3872C>T · rs371205644 · VCV1489365

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0677 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0184%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microphthalmia, syndromic 2

Computational evidence

Protein change
AlphaMissense	0.0677	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -6.06	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.4	GERP 0.68, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 2,355 bp · p 0.26 · regional, not allelic
Overall
CADD	18.62	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 0.0184% African / African-American · 10/54,325 alleles

Filtering AF 0.00997% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00755%

Overall 0.00163% 19/1,163,892 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0184%	5,433
European (non-Finnish)	0.00103%	96,954

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.Pro1291Leu
Coding: c.3872C>T
MANE Select: NM_001123385
dbSNP: rs371205644
Type: single nucleotide variant
Location: chrX:40063047 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 1291: 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.Pro1291Ser Uncertain significance ★ ⚠ same residue
BCOR p.Pro1291= Likely benign ★★ 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

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-pro1291leu (accessed [today's date]).

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