Is BCOR p.Gly421Ser (c.1261G>A) pathogenic?

BCOR p.Gly421Ser (c.1261G>A) is classified Uncertain significance in BCOR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-03). AlphaMissense: likely benign (0.0721); Very rare (popmax 0.00871%, afr); Associated with Inborn genetic diseases.

What condition is associated with BCOR p.Gly421Ser (c.1261G>A)?

BCOR p.Gly421Ser (c.1261G>A) is associated with Inborn genetic diseases (ClinVar).

How common is BCOR p.Gly421Ser (c.1261G>A) in the general population?

BCOR p.Gly421Ser (c.1261G>A) is very rare (popmax 0.00871%, afr) (gnomAD).

What do computational predictors say about BCOR p.Gly421Ser (c.1261G>A)?

AlphaMissense predicts likely benign (score 0.0721) — an in-silico prediction, not a clinical call.

BCOR p.Gly421Ser

c.1261G>A · VCV3824046

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0721 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00871%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0721	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -4.83	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 3.4	GERP 0.51, phastCons 0.2
Regional constraint	o/e 0.90	unconstrained · MANE · 2,116 bp · p 0.013 · regional, not allelic
Overall
CADD	12.32	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 0.00871% African / African-American · 5/57,392 alleles

Filtering AF 0.00337% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00215%

Overall 0.0014% 17/1,210,522 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00871%	11,478
Remaining individualsnot grpmax-eligible	0.0084%	11,902
Admixed American	0.00653%	15,306
South Asian	0.00176%	56,853
European (non-Finnish)	0.000447%	223,833

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.Gly421Ser
Coding: c.1261G>A
MANE Select: NM_001123385
Type: single nucleotide variant
Location: chrX:40074085 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 421: 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

Similar variants

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BCOR p.Arg763Trp Uncertain significance ★★ ⚠ same condition
BCOR p.Asn193Ser Uncertain significance ★★ ⚠ same condition
BCOR p.Asp1420Asn 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-gly421ser (accessed [today's date]).

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