Is BCOR p.Lys419= (c.1257A>G) pathogenic?

BCOR p.Lys419= (c.1257A>G) is classified Benign/Likely benign in BCOR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-15). Rare (popmax 0.976%, sas); Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Lys419= (c.1257A>G)?

BCOR p.Lys419= (c.1257A>G) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Lys419= (c.1257A>G) in the general population?

BCOR p.Lys419= (c.1257A>G) is rare (popmax 0.976%, sas) (gnomAD).

BCOR p.Lys419=

c.1257A>G · rs531585800 · VCV696480

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.976%, sas)

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 0.44	GERP -0.49, phastCons 1
Overall
CADD	1.828	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.976% South Asian · 555/56,881 alleles

Filtering AF 0.909% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.882%

Overall 0.0496% 601/1,210,852 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.976%	102
Middle Eastern	0.115%	871
Remaining individualsnot grpmax-eligible	0.084%	1,191
European (non-Finnish)	0.000112%	895,343

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.Lys419=
Coding: c.1257A>G
MANE Select: NM_001123385
dbSNP: rs531585800
Type: single nucleotide variant
Location: chrX:40074089 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 419: 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-lys419 (accessed [today's date]).

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