Is BRIP1 p.Asn1028= (c.3084T>C) pathogenic?

BRIP1 p.Asn1028= (c.3084T>C) is classified Benign/Likely benign in BRIP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-13). Very rare (popmax 0.00237%, nfe); Associated with familial ovarian cancer.

What condition is associated with BRIP1 p.Asn1028= (c.3084T>C)?

BRIP1 p.Asn1028= (c.3084T>C) is associated with familial ovarian cancer, Fanconi anemia complementation group J, hereditary neoplastic syndrome (ClinVar).

How common is BRIP1 p.Asn1028= (c.3084T>C) in the general population?

BRIP1 p.Asn1028= (c.3084T>C) is very rare (popmax 0.00237%, nfe) (gnomAD).

BRIP1 p.Asn1028=

c.3084T>C · rs1424179519 · VCV461136

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00237%, nfe)

Conditions

familial ovarian cancer

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.059	GERP -4
Overall
CADD	0.749	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00237% European (non-Finnish) · 28/1,180,030 alleles

Filtering AF 0.00164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00198% 29/1,461,874 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00237%	42,144
Remaining individualsnot grpmax-eligible	0.0016%	62,508

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.Asn1028=
Coding: c.3084T>C
MANE Select: NM_032043
dbSNP: rs1424179519
Type: single nucleotide variant
Location: chr17:61683962 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 1028: the 'interaction with brca1' region; the 'disordered' region

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

Disease context

familial ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Fanconi anemia complementation group J hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

BRIP1 p.Asn1028Ile Uncertain significance ★★ ⚠ same residue
BRIP1 p.Asn1028Lys Uncertain significance ★★ ⚠ same residue
BRIP1 p.Asn1028Ser Uncertain significance ★★ ⚠ same residue
BRIP1 p.Asn1028Thr Uncertain significance ★★ ⚠ same residue
BRIP1 p.Asn1028Asp Uncertain significance ★ ⚠ same residue
BRIP1 c.1140+1G>A Likely pathogenic ★★ same condition
BRIP1 c.1141-2A>C Likely pathogenic ★★ same condition
BRIP1 c.1141-2A>G 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-asn1028 (accessed [today's date]).

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