Is BCOR p.Leu808Phe (c.2422C>T) pathogenic?

BCOR p.Leu808Phe (c.2422C>T) is classified Conflicting classifications of pathogenicity in BCOR (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-06). AlphaMissense: likely benign (0.2779); Very rare (popmax 0.00591%, eas); Associated with Inborn genetic diseases.

What condition is associated with BCOR p.Leu808Phe (c.2422C>T)?

BCOR p.Leu808Phe (c.2422C>T) is associated with Inborn genetic diseases, microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Leu808Phe (c.2422C>T) in the general population?

BCOR p.Leu808Phe (c.2422C>T) is very rare (popmax 0.00591%, eas) (gnomAD).

What do computational predictors say about BCOR p.Leu808Phe (c.2422C>T)?

AlphaMissense predicts likely benign (score 0.2779) — an in-silico prediction, not a clinical call.

BCOR p.Leu808Phe

c.2422C>T · rs1459369528 · VCV2304898

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2779 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00591%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2779	likely benign
REVEL	0.3	indeterminate
SaProt	LLR -8.22	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 2,116 bp · p 0.013 · regional, not allelic
Overall
CADD	23.2	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 0.00591% East Asian · 2/33,843 alleles

Filtering AF 0.000979% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000364% 4/1,098,057 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00591%	16,922
Remaining individualsnot grpmax-eligible	0.0042%	23,825

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.Leu808Phe
Coding: c.2422C>T
MANE Select: NM_001123385
dbSNP: rs1459369528
Type: single nucleotide variant
Location: chrX:40072924 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB

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.Leu808His Benign/Likely benign ★★ same residue
BCOR p.Leu808= Benign/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.Arg810Ter Pathogenic ★★ same condition
BCOR p.Arg976Ter Pathogenic ★★ 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-leu808phe (accessed [today's date]).

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