Is BCOR p.Ala1312= (c.3936A>G) pathogenic?

BCOR p.Ala1312= (c.3936A>G) is classified Likely benign in BCOR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-03). Very rare (popmax 0.000227%, nfe); Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Ala1312= (c.3936A>G)?

BCOR p.Ala1312= (c.3936A>G) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Ala1312= (c.3936A>G) in the general population?

BCOR p.Ala1312= (c.3936A>G) is very rare (popmax 0.000227%, nfe) (gnomAD).

BCOR p.Ala1312=

c.3936A>G · rs2519603241 · VCV1952228

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000227%, nfe)

Conditions

microphthalmia, syndromic 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.023	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.079	GERP -3.5, phastCons 0.92
Overall
CADD	7.776	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000227% European (non-Finnish) · 2/880,134 alleles

Filtering AF 3.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000187% 2/1,068,711 alleles · very rare

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.Ala1312=
Coding: c.3936A>G
MANE Select: NM_001123385
dbSNP: rs2519603241
Type: single nucleotide variant
Location: chrX:40062983 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB
Residue 1312: 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-ala1312 (accessed [today's date]).

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