Is BRIP1 p.Arg798Gln (c.2393G>A) pathogenic?

BRIP1 p.Arg798Gln (c.2393G>A) is classified Uncertain significance in BRIP1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.1702); Very rare (popmax 0.00154%, nfe); Associated with hereditary breast carcinoma.

What condition is associated with BRIP1 p.Arg798Gln (c.2393G>A)?

BRIP1 p.Arg798Gln (c.2393G>A) is associated with hereditary breast carcinoma, ovarian cancer, Fanconi anemia complementation group J (ClinVar).

How common is BRIP1 p.Arg798Gln (c.2393G>A) in the general population?

BRIP1 p.Arg798Gln (c.2393G>A) is very rare (popmax 0.00154%, nfe) (gnomAD).

How is Hereditary breast cancer inherited?

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

What do computational predictors say about BRIP1 p.Arg798Gln (c.2393G>A)?

AlphaMissense predicts likely benign (score 0.1702) — an in-silico prediction, not a clinical call.

BRIP1 p.Arg798Gln

c.2393G>A · rs375082407 · VCV142949

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.1702 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00154%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
AlphaMissense	0.1702	likely benign
REVEL	0.462	indeterminate
SaProt	LLR -9.95	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 1.5, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 110 kb · p 3.3e-06 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00154% European (non-Finnish) · 18/1,167,500 alleles

Filtering AF 0.000964% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000795%

Overall 0.00138% 22/1,592,810 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00317%	31,534
Remaining individualsnot grpmax-eligible	0.00162%	61,554
European (non-Finnish)grpmax	0.00154%	64,861
South Asian	0.00116%	86,134

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg798Gln
Coding: c.2393G>A
MANE Select: NM_032043
dbSNP: rs375082407
Type: single nucleotide variant
Location: chr17:61716050 (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: ovarian cancer 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.Arg798Ter Pathogenic/Likely pathogenic ★★ same residue
BRIP1 p.Arg798Pro Uncertain significance ★ ⚠ same residue
BRIP1 p.Arg798= Likely benign ★ same residue
BRIP1 p.Arg798fs Pathogenic ★★ 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
BRIP1 c.1141-2A>T 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-arg798gln (accessed [today's date]).

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