Is BCOR p.His597= (c.1791C>T) pathogenic?

BCOR p.His597= (c.1791C>T) is classified Benign/Likely benign in BCOR (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-02). Common (popmax 6.09%, mid) — too common for a highly-penetrant pathogenic allele; Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.His597= (c.1791C>T)?

BCOR p.His597= (c.1791C>T) is associated with microphthalmia, syndromic 2 (ClinVar).

BCOR p.His597=

Q: How common is BCOR p.His597= (c.1791C>T) in the general population?

BCOR p.His597= (c.1791C>T) is common (popmax 6.09%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1791C>T · rs144606152 · VCV95767

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 6.09%, mid) — too common for a highly-penetrant pathogenic allele

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 -2.9	GERP -3.5
Overall
CADD	0.477	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.09% Middle Eastern · 265/4,354 alleles

Filtering AF 5.48% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.25%

Overall 4.36% 52,764/1,211,156 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	6.09%	16
Ashkenazi Jewishnot grpmax-eligible	6.08%	16
European (non-Finnish)	5.06%	20
Remaining individualsnot grpmax-eligible	4.26%	23
Finnishnot grpmax-eligible	3.81%	26
Admixed American	1.95%	51
South Asian	1.39%	72
Amishnot grpmax-eligible	1.31%	76
African / African-American	0.661%	151
East Asian	0.00888%	11,263

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.His597=
Coding: c.1791C>T
MANE Select: NM_001123385
dbSNP: rs144606152
Type: single nucleotide variant
Location: chrX:40073555 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 597: 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.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-his597 (accessed [today's date]).

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