Is BCOR p.Thr75Ser (c.223A>T) pathogenic?

BCOR p.Thr75Ser (c.223A>T) is classified Likely benign in BCOR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-18). AlphaMissense: likely benign (0.076); Rare (popmax 0.187%, afr); Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Thr75Ser (c.223A>T)?

BCOR p.Thr75Ser (c.223A>T) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Thr75Ser (c.223A>T) in the general population?

BCOR p.Thr75Ser (c.223A>T) is rare (popmax 0.187%, afr) (gnomAD).

What do computational predictors say about BCOR p.Thr75Ser (c.223A>T)?

AlphaMissense predicts likely benign (score 0.076) — an in-silico prediction, not a clinical call.

BCOR p.Thr75Ser

c.223A>T · rs61744882 · VCV581701

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.076 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.187%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microphthalmia, syndromic 2

Computational evidence

Protein change
AlphaMissense	0.076	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -5.60	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 1.2	GERP 0.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 3,243 bp · p 0.27 · regional, not allelic
Overall
CADD	8.429	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 0.187% African / African-American · 106/56,730 alleles

Filtering AF 0.158% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.147%

Overall 0.00894% 108/1,208,035 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.187%	535
Admixed American	0.00219%	45,591
Remaining individualsnot grpmax-eligible	0.0021%	47,567

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.Thr75Ser
Coding: c.223A>T
MANE Select: NM_001123385
dbSNP: rs61744882
Type: single nucleotide variant
Location: chrX:40075123 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB

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

Disease context

microphthalmia, syndromic 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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BCOR p.Arg1514Ter Pathogenic ★★ same condition
BCOR p.Arg342Ter Pathogenic ★★ same condition
BCOR p.Arg976Ter Pathogenic ★★ same condition
BCOR p.Ala1262Ser Uncertain significance ★★ ⚠ same condition
BCOR p.Ala1307Pro Uncertain significance ★★ ⚠ same condition
BCOR p.Ala165Pro 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-thr75ser (accessed [today's date]).

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