Is BCOR p.Tyr985Phe (c.2954A>T) pathogenic?

BCOR p.Tyr985Phe (c.2954A>T) is classified Uncertain significance in BCOR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-11-15). AlphaMissense: likely pathogenic (0.5642); Ultra-rare (popmax 0.0233%, mid); Associated with Inborn genetic diseases.

What condition is associated with BCOR p.Tyr985Phe (c.2954A>T)?

BCOR p.Tyr985Phe (c.2954A>T) is associated with Inborn genetic diseases, microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Tyr985Phe (c.2954A>T) in the general population?

BCOR p.Tyr985Phe (c.2954A>T) is ultra-rare (popmax 0.0233%, mid) (gnomAD).

What do computational predictors say about BCOR p.Tyr985Phe (c.2954A>T)?

AlphaMissense predicts likely pathogenic (score 0.5642) — an in-silico prediction, not a clinical call.

BCOR p.Tyr985Phe

c.2954A>T · rs587778093 · VCV133679

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.5642 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0233%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5642	likely pathogenic
REVEL	0.189	benign-leaning
SaProt	LLR -5.65	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 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 7,889 bp · p 9.6e-07 · regional, not allelic
Overall
CADD	24.9	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 0.0233% Middle Eastern · 1/4,299 alleles

Filtering AF 0.00941% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00721%

Overall 0.00108% 13/1,208,648 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0233%	4,299
African / African-American	0.0175%	5,718
South Asian	0.00177%	56,437
European (non-Finnish)	0.000112%	894,478

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.Tyr985Phe
Coding: c.2954A>T
MANE Select: NM_001123385
dbSNP: rs587778093
Type: single nucleotide variant
Location: chrX:40072392 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB

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

Also linked: microphthalmia, syndromic 2

Similar variants

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BCOR p.Arg810Ter 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-tyr985phe (accessed [today's date]).

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