Is BCOR p.Pro1116Ser (c.3346C>T) pathogenic?

BCOR p.Pro1116Ser (c.3346C>T) is classified Conflicting classifications of pathogenicity in BCOR (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-30). AlphaMissense: likely benign (0.0656); Ultra-rare (popmax 0.0109%, amr); Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Pro1116Ser (c.3346C>T)?

BCOR p.Pro1116Ser (c.3346C>T) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Pro1116Ser (c.3346C>T) in the general population?

BCOR p.Pro1116Ser (c.3346C>T) is ultra-rare (popmax 0.0109%, amr) (gnomAD).

What do computational predictors say about BCOR p.Pro1116Ser (c.3346C>T)?

AlphaMissense predicts likely benign (score 0.0656) — an in-silico prediction, not a clinical call.

BCOR p.Pro1116Ser

c.3346C>T · rs140923855 · VCV2193564

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0656 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0109%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microphthalmia, syndromic 2

Computational evidence

Protein change
AlphaMissense	0.0656	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -5.71	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 2.7	GERP 0.62, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 2,355 bp · p 0.26 · regional, not allelic
Overall
CADD	6.454	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 0.0109% Admixed American · 5/46,000 alleles

Filtering AF 0.00426% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0027%

Overall 0.00388% 47/1,211,072 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0109%	9,200
Remaining individualsnot grpmax-eligible	0.0105%	9,523
European (non-Finnish)	0.00413%	24,201

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.Pro1116Ser
Coding: c.3346C>T
MANE Select: NM_001123385
dbSNP: rs140923855
Type: single nucleotide variant
Location: chrX:40064492 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 1116: the 'disordered' region

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.Pro1116= Likely benign ★★ same residue
BCOR p.Pro1116Thr 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

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-pro1116ser (accessed [today's date]).

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