Is BCOR p.Arg1699Gln (c.5096G>A) pathogenic?

BCOR p.Arg1699Gln (c.5096G>A) is classified Uncertain significance in BCOR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-20). AlphaMissense: likely benign (0.1549); Very rare (popmax 0.0038%, nfe); Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Arg1699Gln (c.5096G>A)?

BCOR p.Arg1699Gln (c.5096G>A) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Arg1699Gln (c.5096G>A) in the general population?

BCOR p.Arg1699Gln (c.5096G>A) is very rare (popmax 0.0038%, nfe) (gnomAD).

What do computational predictors say about BCOR p.Arg1699Gln (c.5096G>A)?

AlphaMissense predicts likely benign (score 0.1549) — an in-silico prediction, not a clinical call.

BCOR p.Arg1699Gln

c.5096G>A · VCV3603863

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1549 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0038%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microphthalmia, syndromic 2

Computational evidence

Protein change
AlphaMissense	0.1549	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -8.74	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 4	GERP 1.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 3,308 bp · p 0.29 · regional, not allelic
Overall
CADD	22.7	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 0.0038% European (non-Finnish) · 34/895,360 alleles

Filtering AF 0.00273% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.00339% 41/1,210,451 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0038%	26,334
South Asian	0.00352%	28,430
African / African-American	0.00349%	28,651
East Asian	0.00296%	33,809
Admixed American	0.00218%	45,797
Remaining individualsnot grpmax-eligible	0.0021%	47,596

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.Arg1699Gln
Coding: c.5096G>A
MANE Select: NM_001123385
Type: single nucleotide variant
Location: chrX:40052281 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 1699: the 'necessary and sufficient for interaction with pcgf1' region; an α-helix

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
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
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-arg1699gln (accessed [today's date]).

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