Is BCOR p.Pro1648Leu (c.4943C>T) pathogenic?

BCOR p.Pro1648Leu (c.4943C>T) is classified Conflicting classifications of pathogenicity in BCOR (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-09-24). AlphaMissense: likely pathogenic (0.859); Very rare (popmax 0.00529%, sas); Associated with Inborn genetic diseases.

What condition is associated with BCOR p.Pro1648Leu (c.4943C>T)?

BCOR p.Pro1648Leu (c.4943C>T) is associated with Inborn genetic diseases, microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Pro1648Leu (c.4943C>T) in the general population?

BCOR p.Pro1648Leu (c.4943C>T) is very rare (popmax 0.00529%, sas) (gnomAD).

What do computational predictors say about BCOR p.Pro1648Leu (c.4943C>T)?

AlphaMissense predicts likely pathogenic (score 0.859) — an in-silico prediction, not a clinical call.

BCOR p.Pro1648Leu

c.4943C>T · rs763651353 · VCV2074957

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.859 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00529%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.859	likely pathogenic
REVEL	0.545	indeterminate
SaProt	LLR -7.36	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 3,308 bp · p 0.29 · regional, not allelic
Overall
CADD	24.3	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 0.00529% South Asian · 3/56,681 alleles

Filtering AF 0.0014% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000689%

Overall 0.000993% 12/1,209,023 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00529%	18,894
African / African-American	0.00526%	19,012
East Asian	0.00296%	33,762
Admixed American	0.00219%	45,614
Remaining individualsnot grpmax-eligible	0.0021%	47,584
European (non-Finnish)	0.000335%	298,270

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.Pro1648Leu
Coding: c.4943C>T
MANE Select: NM_001123385
dbSNP: rs763651353
Type: single nucleotide variant
Location: chrX:40053919 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 1648: 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

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

Also linked: microphthalmia, syndromic 2

Similar variants

BCOR p.Pro1648= Likely benign ★★ same residue
BCOR p.Pro1648Arg 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

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-pro1648leu (accessed [today's date]).

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