Is BCOR p.Arg1375Trp (c.4123C>T) pathogenic?

BCOR p.Arg1375Trp (c.4123C>T) is classified Uncertain significance in BCOR (ClinVar, Single submitter, 3 submitters; last evaluated 2022-05-28). AlphaMissense: likely benign (0.1667); Absent from gnomAD v4.1; Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Arg1375Trp (c.4123C>T)?

BCOR p.Arg1375Trp (c.4123C>T) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Arg1375Trp (c.4123C>T) in the general population?

BCOR p.Arg1375Trp (c.4123C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BCOR p.Arg1375Trp (c.4123C>T)?

AlphaMissense predicts likely benign (score 0.1667) — an in-silico prediction, not a clinical call.

BCOR p.Arg1375Trp

c.4123C>T · rs1343680559 · VCV2170072

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1667 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microphthalmia, syndromic 2

Computational evidence

Protein change
AlphaMissense	0.1667	likely benign
REVEL	0.244	benign-leaning
SaProt	LLR -8.67	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.79	donor gain · deltas
Pangolin	Δ0.34	gain · loss 0.10 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.3	GERP -0.67, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 2,355 bp · p 0.26 · regional, not allelic
Overall
CADD	31.0	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.Arg1375Trp
Coding: c.4123C>T
MANE Select: NM_001123385
dbSNP: rs1343680559
Type: single nucleotide variant
Location: chrX:40062796 (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
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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-arg1375trp (accessed [today's date]).

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