Is BRIP1 p.Leu36fs (c.106_107insG) pathogenic?

BRIP1 p.Leu36fs (c.106107insG) is classified Pathogenic in BRIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-21). Absent from gnomAD; Associated with hereditary breast carcinoma.

What condition is associated with BRIP1 p.Leu36fs (c.106_107insG)?

BRIP1 p.Leu36fs (c.106_107insG) is associated with hereditary breast carcinoma (ClinVar).

How common is BRIP1 p.Leu36fs (c.106_107insG) in the general population?

BRIP1 p.Leu36fs (c.106_107insG) 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.Leu36fs

c.106_107insG · rs2545473339 · VCV2583850

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

hereditary breast carcinoma

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 3 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1

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: BRIP1
Protein: p.Leu36fs
Coding: c.106_107insG
MANE Select: NM_032043
dbSNP: rs2545473339
Type: Insertion
Location: chr17:61859894 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 36: the helicase atp-binding domain

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

For Hereditary breast cancer (Orphanet):

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

Similar variants

BRIP1 p.Leu36Phe Uncertain significance ★★ ⚠ same residue
BRIP1 p.Leu36= Benign/Likely benign ★★ same residue
BRIP1 p.Leu36Ter Pathogenic ★ same residue
BRIP1 p.Leu36Ser Uncertain significance ★ ⚠ same residue
BRIP1 p.Asp566_Lys567insIleSerAsnTer Pathogenic ★★ same condition
BRIP1 p.Leu340fs Pathogenic/Likely pathogenic ★★ same condition
BRIP1 p.Pro619fs Pathogenic/Likely pathogenic ★★ same condition
BRIP1 p.Ser215fs 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-leu36fs (accessed [today's date]).

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