Is BCOR p.Arg1681His (c.5042G>A) pathogenic?

BCOR p.Arg1681His (c.5042G>A) is classified Conflicting classifications of pathogenicity in BCOR (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-09-22). AlphaMissense: ambiguous (0.3577); Very rare (popmax 0.00888%, eas); Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Arg1681His (c.5042G>A)?

BCOR p.Arg1681His (c.5042G>A) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Arg1681His (c.5042G>A) in the general population?

BCOR p.Arg1681His (c.5042G>A) is very rare (popmax 0.00888%, eas) (gnomAD).

What do computational predictors say about BCOR p.Arg1681His (c.5042G>A)?

AlphaMissense predicts ambiguous (score 0.3577) — an in-silico prediction, not a clinical call.

BCOR p.Arg1681His

c.5042G>A · rs372913827 · VCV976181

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3577 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00888%, eas)

Conditions

microphthalmia, syndromic 2

Computational evidence

Protein change
AlphaMissense	0.3577	ambiguous
REVEL	0.36	indeterminate
SaProt	LLR -8.99	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 3,308 bp · p 0.29 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00888% East Asian · 3/33,798 alleles

Filtering AF 0.00235% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00125%

Overall 0.000661% 8/1,210,109 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00888%	11,266
African / African-American	0.00349%	28,644
European (non-Finnish)	0.000335%	298,370

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.Arg1681His
Coding: c.5042G>A
MANE Select: NM_001123385
dbSNP: rs372913827
Type: single nucleotide variant
Location: chrX:40052335 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 1681: 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.Arg1681Cys Uncertain significance ★ ⚠ 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-arg1681his (accessed [today's date]).

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