Is BCOR p.Pro1648= (c.4944G>A) pathogenic?

BCOR p.Pro1648= (c.4944G>A) is classified Likely benign in BCOR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-10). Very rare (popmax 0.00219%, amr); Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Pro1648= (c.4944G>A)?

BCOR p.Pro1648= (c.4944G>A) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Pro1648= (c.4944G>A) in the general population?

BCOR p.Pro1648= (c.4944G>A) is very rare (popmax 0.00219%, amr) (gnomAD).

BCOR p.Pro1648=

c.4944G>A · rs1479323402 · VCV1094409

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00219%, amr)

Conditions

microphthalmia, syndromic 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14	GERP -3.8
Overall
CADD	0.026	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00219% Admixed American · 1/45,628 alleles

Filtering AF 0.000241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000158%

Overall 0.000662% 8/1,209,288 alleles · very rare exomes 5/1,097,726 · genomes 3/111,562 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00219%	45,628
Remaining individualsnot grpmax-eligible	0.0021%	47,584
European (non-Finnish)	0.00067%	149,161

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.Pro1648=
Coding: c.4944G>A
MANE Select: NM_001123385
dbSNP: rs1479323402
Type: single nucleotide variant
Location: chrX:40053918 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 1648: the 'necessary and sufficient for interaction with pcgf1' region; an α-helix

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.Pro1648Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
BCOR p.Pro1648Arg 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-pro1648 (accessed [today's date]).

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