Is BCOR p.Pro602Leu (c.1805C>T) pathogenic?

BCOR p.Pro602Leu (c.1805C>T) is classified Uncertain significance in BCOR (ClinVar, Single submitter, 1 submitter; last evaluated 2017-11-10). AlphaMissense: likely benign (0.0711); Ultra-rare (popmax 0.0266%, eas).

How common is BCOR p.Pro602Leu (c.1805C>T) in the general population?

BCOR p.Pro602Leu (c.1805C>T) is ultra-rare (popmax 0.0266%, eas) (gnomAD).

What do computational predictors say about BCOR p.Pro602Leu (c.1805C>T)?

AlphaMissense predicts likely benign (score 0.0711) — an in-silico prediction, not a clinical call.

BCOR p.Pro602Leu

c.1805C>T · rs766045784 · VCV1336335

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0711 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0266%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0711	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -6.93	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 5.2	GERP 0.66, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 2,116 bp · p 0.013 · regional, not allelic
Overall
CADD	16.23	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 0.0266% East Asian · 9/33,800 alleles

Filtering AF 0.0139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0103%

Overall 0.00132% 16/1,210,995 alleles · ultra-rare exomes 12/1,097,858 · genomes 4/113,137 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0266%	3,756
Middle Eastern	0.0229%	4,374
Remaining individualsnot grpmax-eligible	0.0063%	15,873
Finnishnot grpmax-eligible	0.00215%	46,498
African / African-American	0.00174%	57,586
European (non-Finnish)	0.000112%	895,472

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.Pro602Leu
Coding: c.1805C>T
MANE Select: NM_001123385
dbSNP: rs766045784
Type: single nucleotide variant
Location: chrX:40073541 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 602: the 'disordered' region

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

Similar variants

BCOR p.Pro602= Likely benign ★ same residue
BCOR p.Arg1163Ter Pathogenic ★★ same type
BCOR p.Arg1164Ter Pathogenic ★★ same type
BCOR p.Arg1217Ter Pathogenic ★★ same type
BCOR p.Arg1514Ter Pathogenic ★★ same type
BCOR p.Arg342Ter Pathogenic ★★ same type
BCOR p.Arg810Ter Pathogenic ★★ same type
BCOR p.Arg976Ter Pathogenic ★★ same type

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-pro602leu (accessed [today's date]).

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