Is BCOR p.Lys1325Arg (c.3974A>G) pathogenic?

BCOR p.Lys1325Arg (c.3974A>G) is classified Benign/Likely benign in BCOR (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-15). AlphaMissense: likely benign (0.0799); Rare (popmax 0.737%, amr); Associated with Inborn genetic diseases.

What condition is associated with BCOR p.Lys1325Arg (c.3974A>G)?

BCOR p.Lys1325Arg (c.3974A>G) is associated with Inborn genetic diseases, microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Lys1325Arg (c.3974A>G) in the general population?

BCOR p.Lys1325Arg (c.3974A>G) is rare (popmax 0.737%, amr) (gnomAD).

What do computational predictors say about BCOR p.Lys1325Arg (c.3974A>G)?

AlphaMissense predicts likely benign (score 0.0799) — an in-silico prediction, not a clinical call.

BCOR p.Lys1325Arg

c.3974A>G · rs187172641 · VCV133695

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0799 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.737%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0799	likely benign
REVEL	0.158	moderately benign-leaning
SaProt	LLR -6.52	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 6.1	GERP 1.7, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 2,355 bp · p 0.26 · regional, not allelic
Overall
CADD	20.6	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 0.737% Admixed American · 329/44,664 alleles

Filtering AF 0.671% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.645%

Overall 0.0293% 352/1,200,919 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.737%	136
Remaining individualsnot grpmax-eligible	0.0275%	3,637
African / African-American	0.0123%	8,158
European (non-Finnish)	0.000337%	296,679

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.Lys1325Arg
Coding: c.3974A>G
MANE Select: NM_001123385
dbSNP: rs187172641
Type: single nucleotide variant
Location: chrX:40062945 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 1325: 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.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
BCOR p.Ala1307Pro 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-lys1325arg (accessed [today's date]).

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