Is BCOR p.Met1575Thr (c.4724T>C) pathogenic?

BCOR p.Met1575Thr (c.4724T>C) is classified Conflicting classifications of pathogenicity in BCOR (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-04-01). AlphaMissense: likely pathogenic (0.9847); Ultra-rare (popmax 0.0733%, afr); Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Met1575Thr (c.4724T>C)?

BCOR p.Met1575Thr (c.4724T>C) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Met1575Thr (c.4724T>C) in the general population?

BCOR p.Met1575Thr (c.4724T>C) is ultra-rare (popmax 0.0733%, afr) (gnomAD).

What do computational predictors say about BCOR p.Met1575Thr (c.4724T>C)?

AlphaMissense predicts likely pathogenic (score 0.9847) — an in-silico prediction, not a clinical call.

BCOR p.Met1575Thr

c.4724T>C · rs142595337 · VCV194101

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely pathogenic

0.9847 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0733%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

microphthalmia, syndromic 2

Computational evidence

Protein change
AlphaMissense	0.9847	likely pathogenic · top 7% in BCOR
REVEL	0.577	indeterminate
SaProt	LLR -11.98	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.58 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 3,308 bp · p 0.29 · regional, not allelic
Overall
CADD	24.1	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 0.0733% African / African-American · 42/57,303 alleles

Filtering AF 0.0557% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0495%

Overall 0.00777% 94/1,209,859 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0733%	1,364
Admixed American	0.072%	1,388
Remaining individualsnot grpmax-eligible	0.0231%	4,328
South Asian	0.00176%	56,835
European (non-Finnish)	0.000782%	127,829

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.Met1575Thr
Coding: c.4724T>C
MANE Select: NM_001123385
dbSNP: rs142595337
Type: single nucleotide variant
Location: chrX:40055385 (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

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.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-met1575thr (accessed [today's date]).

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