Is BRIP1 p.Arg431Ter (c.1289_1290dup) pathogenic?

BRIP1 p.Arg431Ter (c.12891290dup) is classified Pathogenic in BRIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-22). Absent from gnomAD; Associated with hereditary breast carcinoma.

What condition is associated with BRIP1 p.Arg431Ter (c.1289_1290dup)?

BRIP1 p.Arg431Ter (c.1289_1290dup) is associated with hereditary breast carcinoma, Fanconi anemia complementation group J (ClinVar).

How common is BRIP1 p.Arg431Ter (c.1289_1290dup) in the general population?

BRIP1 p.Arg431Ter (c.1289_1290dup) 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.Arg431Ter

c.1289_1290dup · rs2145302423 · VCV1068821

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

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	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 9 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.6	GERP 0.98, 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.Arg431Ter
Coding: c.1289_1290dup
MANE Select: NM_032043
dbSNP: rs2145302423
Type: Microsatellite
Location: chr17:61799149 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 431: 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

Also linked: Fanconi anemia complementation group J

For Hereditary breast cancer (Orphanet):

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

Similar variants

BRIP1 p.Arg431Lys Uncertain significance ★★ ⚠ same residue
BRIP1 p.Arg431= Benign/Likely benign ★★ same residue
BRIP1 p.Arg431Trp Uncertain significance ★ ⚠ same residue
BRIP1 c.1340+2_1340+5del Likely pathogenic ★★ same condition
BRIP1 c.2492_2492+3del Likely pathogenic ★★ same condition
BRIP1 p.Ala402fs Pathogenic ★★ same condition
BRIP1 p.Asn97fs Pathogenic ★★ same condition
BRIP1 p.Asp460fs 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-arg431ter (accessed [today's date]).

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