Is BCOR p.Ala275fs (c.821dup) pathogenic?

BCOR p.Ala275fs (c.821dup) is classified Pathogenic in BCOR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-13). Absent from gnomAD; Associated with microphthalmia, syndromic 2.

What condition is associated with BCOR p.Ala275fs (c.821dup)?

BCOR p.Ala275fs (c.821dup) is associated with microphthalmia, syndromic 2 (ClinVar).

How common is BCOR p.Ala275fs (c.821dup) in the general population?

BCOR p.Ala275fs (c.821dup) is absent from gnomAD (gnomAD).

BCOR p.Ala275fs

c.821dup · rs2520083089 · VCV2820321

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

microphthalmia, syndromic 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -4.7	GERP -3.2

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BCOR
Protein: p.Ala275fs
Coding: c.821dup
MANE Select: NM_001123385
dbSNP: rs2520083089
Type: Duplication
Location: chrX:40074524 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB

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.Leu1646fs Pathogenic/Likely pathogenic ★★ same condition
BCOR p.Ala1224fs Pathogenic ★ same condition
BCOR p.Gln1306fs Pathogenic ★ same condition
BCOR p.Leu1130fs Pathogenic ★ same condition
BCOR p.Leu1214fs Likely pathogenic ★ same condition
BCOR p.Pro512delinsLysTrpLeuCysTyrLeuTer Pathogenic ★ same condition
BCOR p.Tyr1082fs Pathogenic ★ same condition
BCOR p.Tyr1601fs Likely pathogenic ★ 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-ala275fs (accessed [today's date]).

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