Is BCOR p.Thr819Ser (c.2455A>T) pathogenic?

BCOR p.Thr819Ser (c.2455A>T) is classified Uncertain significance in BCOR (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-04). AlphaMissense: likely benign (0.0777); Very rare (popmax 0.000893%, nfe); Associated with intellectual disability.

What condition is associated with BCOR p.Thr819Ser (c.2455A>T)?

BCOR p.Thr819Ser (c.2455A>T) is associated with intellectual disability (ClinVar).

How common is BCOR p.Thr819Ser (c.2455A>T) in the general population?

BCOR p.Thr819Ser (c.2455A>T) is very rare (popmax 0.000893%, nfe) (gnomAD).

What do computational predictors say about BCOR p.Thr819Ser (c.2455A>T)?

AlphaMissense predicts likely benign (score 0.0777) — an in-silico prediction, not a clinical call.

BCOR p.Thr819Ser

c.2455A>T · VCV4074802

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0777 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000893%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.0777	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -5.72	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 -1.5	GERP -3.4
Regional constraint	o/e 0.90	unconstrained · MANE · 2,116 bp · p 0.013 · regional, not allelic
Overall
CADD	0.037	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 0.000893% European (non-Finnish) · 8/895,443 alleles

Filtering AF 0.000384% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000278%

Overall 0.000728% 8/1,098,243 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.Thr819Ser
Coding: c.2455A>T
MANE Select: NM_001123385
Type: single nucleotide variant
Location: chrX:40072891 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 819: the 'disordered' region

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

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BCOR p.Glu1076Lys Benign/Likely benign ★★ same condition
BCOR c.3847+7G>A Conflicting classifications of pathogenicity ★ same condition
BCOR p.Ala1149Val Conflicting classifications of pathogenicity ★ ⚠ same condition
BCOR p.Gln1074Lys Uncertain significance ★ ⚠ same condition
BCOR p.Leu722Phe Conflicting classifications of pathogenicity ★ ⚠ same condition
BCOR p.Ser1551Cys Likely benign ★ ⚠ same condition
BCOR p.Lys1087Asn Likely benign same condition
BCOR p.Lys1167Arg Likely benign 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-thr819ser (accessed [today's date]).

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