Is BCOR p.Met217Ile (c.651G>A) pathogenic?

BCOR p.Met217Ile (c.651G>A) is classified Conflicting classifications of pathogenicity in BCOR (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-11-01). AlphaMissense: likely pathogenic (0.9153); Very rare (popmax 0.00458%, nfe); Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Met217Ile (c.651G>A)?

BCOR p.Met217Ile (c.651G>A) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Met217Ile (c.651G>A) in the general population?

BCOR p.Met217Ile (c.651G>A) is very rare (popmax 0.00458%, nfe) (gnomAD).

What do computational predictors say about BCOR p.Met217Ile (c.651G>A)?

AlphaMissense predicts likely pathogenic (score 0.9153) — an in-silico prediction, not a clinical call.

BCOR p.Met217Ile

c.651G>A · rs368939471 · VCV931573

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9153 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00458%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microphthalmia, syndromic 2

Computational evidence

Protein change
AlphaMissense	0.9153	likely pathogenic
REVEL	0.273	benign-leaning
SaProt	LLR -6.49	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 3,243 bp · p 0.27 · regional, not allelic
Overall
CADD	24.8	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 0.00458% European (non-Finnish) · 41/895,148 alleles

Filtering AF 0.00341% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00307%

Overall 0.0038% 46/1,209,798 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00458%	21,833
Ashkenazi Jewishnot grpmax-eligible	0.00454%	22,029
Remaining individualsnot grpmax-eligible	0.0042%	23,805
Admixed American	0.00218%	45,835
South Asian	0.00176%	56,809

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.Met217Ile
Coding: c.651G>A
MANE Select: NM_001123385
dbSNP: rs368939471
Type: single nucleotide variant
Location: chrX:40074695 (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.Met217Thr Uncertain significance ★ ⚠ same residue
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

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-met217ile (accessed [today's date]).

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