Is BRIP1 p.Asp563del (c.1687_1689del) pathogenic?

BRIP1 p.Asp563del (c.16871689del) is classified Uncertain significance in BRIP1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-29). Very rare (popmax 6.84e-05%); Associated with Fanconi anemia complementation group J.

What condition is associated with BRIP1 p.Asp563del (c.1687_1689del)?

BRIP1 p.Asp563del (c.1687_1689del) is associated with Fanconi anemia complementation group J, hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is BRIP1 p.Asp563del (c.1687_1689del) in the general population?

BRIP1 p.Asp563del (c.1687_1689del) is very rare (popmax 6.84e-05%) (gnomAD).

BRIP1 p.Asp563del

c.1687_1689del · rs780590493 · VCV234459

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Conditions

Fanconi anemia complementation group J

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.47	GERP -3.2

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,768 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: BRIP1
Protein: p.Asp563del
Coding: c.1687_1689del
MANE Select: NM_032043
dbSNP: rs780590493
Type: Deletion
Location: chr17:61780945 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB

Full BRIP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Fanconi anemia complementation group J — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

BRIP1 p.Asp563= Benign/Likely benign ★★ same residue
BRIP1 p.Asp563Ala Uncertain significance ★ ⚠ same residue
BRIP1 p.Asp563Asn Uncertain significance ★ ⚠ same residue
BRIP1 p.Asp563Glu Uncertain significance ★ ⚠ same residue
BRIP1 p.Asp563Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
BRIP1 p.Asp563Val Uncertain significance ★ ⚠ same residue
BRIP1 c.1629-3_1634del Likely pathogenic ★★ same condition
BRIP1 c.1936del 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/brip1-p-asp563del (accessed [today's date]).

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