Is BCOR p.Val842Ala (c.2525T>C) pathogenic?

BCOR p.Val842Ala (c.2525T>C) is classified Conflicting classifications of pathogenicity in BCOR (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-14). AlphaMissense: likely benign (0.0578); Ultra-rare (popmax 0.0999%, afr); Associated with Inborn genetic diseases.

What condition is associated with BCOR p.Val842Ala (c.2525T>C)?

BCOR p.Val842Ala (c.2525T>C) is associated with Inborn genetic diseases, microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Val842Ala (c.2525T>C) in the general population?

BCOR p.Val842Ala (c.2525T>C) is ultra-rare (popmax 0.0999%, afr) (gnomAD).

What do computational predictors say about BCOR p.Val842Ala (c.2525T>C)?

AlphaMissense predicts likely benign (score 0.0578) — an in-silico prediction, not a clinical call.

BCOR p.Val842Ala

c.2525T>C · rs143119333 · VCV287022

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0578 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0999%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0578	likely benign
REVEL	0.183	benign-leaning
SaProt	LLR -6.15	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 0.67, phastCons 0.81
Regional constraint	o/e 0.90	unconstrained · MANE · 2,116 bp · p 0.013 · regional, not allelic
Overall
CADD	2.67	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 0.0999% African / African-American · 57/57,056 alleles

Filtering AF 0.0791% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0717%

Overall 0.00521% 63/1,209,815 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0999%	1,001
Admixed American	0.00655%	15,267
Remaining individualsnot grpmax-eligible	0.0042%	23,793
European (non-Finnish)	0.000112%	895,175

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.Val842Ala
Coding: c.2525T>C
MANE Select: NM_001123385
dbSNP: rs143119333
Type: single nucleotide variant
Location: chrX:40072821 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 842: the 'disordered' region

Full BCOR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: microphthalmia, syndromic 2

Similar variants

BCOR p.Val842Leu 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.Arg810Ter 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-val842ala (accessed [today's date]).

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