Is BRIP1 p.Arg1085Val (c.3253_3254delinsGT) pathogenic?

BRIP1 p.Arg1085Val (c.32533254delinsGT) is classified Uncertain significance in BRIP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-16). Absent from gnomAD; Associated with hereditary breast carcinoma.

What condition is associated with BRIP1 p.Arg1085Val (c.3253_3254delinsGT)?

BRIP1 p.Arg1085Val (c.3253_3254delinsGT) is associated with hereditary breast carcinoma, Fanconi anemia complementation group J, hereditary neoplastic syndrome (ClinVar).

How common is BRIP1 p.Arg1085Val (c.3253_3254delinsGT) in the general population?

BRIP1 p.Arg1085Val (c.3253_3254delinsGT) is absent from gnomAD (gnomAD).

How is Hereditary breast cancer inherited?

Typically Autosomal dominant, Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

BRIP1 p.Arg1085Val

c.3253_3254delinsGT · rs2061314506 · VCV919631

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary breast carcinoma

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 2.8	GERP 0.83, phastCons 0.21
Regional constraint	o/e 0.84	unconstrained · MANE · 110 kb · p 3.3e-06 · regional, not allelic

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: BRIP1
Protein: p.Arg1085Val
Coding: c.3253_3254delinsGT
MANE Select: NM_032043
dbSNP: rs2061314506
Type: Indel
Location: chr17:61683792 (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

hereditary breast carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Fanconi anemia complementation group J hereditary neoplastic syndrome

For Hereditary breast cancer (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult, Elderly

Similar variants

BRIP1 p.Arg1085Thr Uncertain significance ★★ ⚠ same residue
BRIP1 p.Arg1085Gly Uncertain significance ★ ⚠ same residue
BRIP1 p.Arg1085Ile Uncertain significance ★ ⚠ same residue
BRIP1 p.Arg1085Lys Likely benign ★ same residue
BRIP1 c.204_205+1delinsAGT Likely pathogenic ★★ same condition
BRIP1 c.2380-45_2402delinsTTGACCATTTGAATGGT Likely pathogenic ★★ same condition
BRIP1 c.2398_2400delinsATTTG Pathogenic/Likely pathogenic ★★ same condition
BRIP1 p.His715fs Pathogenic/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/brip1-p-arg1085val (accessed [today's date]).

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