Is BCOR p.Lys1672Glu (c.5014A>G) pathogenic?

BCOR p.Lys1672Glu (c.5014A>G) is classified Uncertain significance in BCOR (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-01-21). AlphaMissense: likely pathogenic (0.7389); Very rare (popmax 0.00525%, afr); Associated with BCOR-related disorder.

What condition is associated with BCOR p.Lys1672Glu (c.5014A>G)?

BCOR p.Lys1672Glu (c.5014A>G) is associated with BCOR-related disorder (ClinVar).

How common is BCOR p.Lys1672Glu (c.5014A>G) in the general population?

BCOR p.Lys1672Glu (c.5014A>G) is very rare (popmax 0.00525%, afr) (gnomAD).

What do computational predictors say about BCOR p.Lys1672Glu (c.5014A>G)?

AlphaMissense predicts likely pathogenic (score 0.7389) — an in-silico prediction, not a clinical call.

BCOR p.Lys1672Glu

c.5014A>G · rs1223567941 · VCV3032039

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7389 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00525%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BCOR-related disorder

Computational evidence

Protein change
AlphaMissense	0.7389	likely pathogenic
REVEL	0.108	moderately benign-leaning
SaProt	LLR -7.52	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 3,308 bp · p 0.29 · regional, not allelic
Overall
CADD	21.0	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 0.00525% African / African-American · 3/57,114 alleles

Filtering AF 0.00139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000686%

Overall 0.000248% 3/1,209,275 alleles · very rare

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.Lys1672Glu
Coding: c.5014A>G
MANE Select: NM_001123385
dbSNP: rs1223567941
Type: single nucleotide variant
Location: chrX:40052363 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 1672: 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

BCOR-related disorder

Similar variants

BCOR p.Arg1217Ter Pathogenic ★★ same condition
BCOR p.Asp174Asn Uncertain significance ★★ ⚠ same condition
BCOR p.Ile730Leu Uncertain significance ★★ ⚠ same condition
BCOR c.4174-2A>G Likely pathogenic ★ same condition
BCOR p.Glu1052Ter Likely pathogenic ★ same condition
BCOR p.Glu1464Ter Likely pathogenic ★ same condition
BCOR p.Gly86Ter Likely pathogenic ★ same condition
BCOR p.Gln156Pro 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-lys1672glu (accessed [today's date]).

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