Is BRIP1 p.Arg798Ter (c.2392C>T) pathogenic?

BRIP1 p.Arg798Ter (c.2392C>T) is classified Pathogenic/Likely pathogenic in BRIP1 (ClinVar, Multiple submitters, 52 submitters; last evaluated 2026-08-06). Ultra-rare (popmax 0.0348%, nfe); Associated with Monogenic short statue.

What condition is associated with BRIP1 p.Arg798Ter (c.2392C>T)?

BRIP1 p.Arg798Ter (c.2392C>T) is associated with Monogenic short statue, gastric cancer, breast cancer (ClinVar).

How common is BRIP1 p.Arg798Ter (c.2392C>T) in the general population?

BRIP1 p.Arg798Ter (c.2392C>T) is ultra-rare (popmax 0.0348%, nfe) (gnomAD).

BRIP1 p.Arg798Ter

c.2392C>T · rs137852986 · VCV4738

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 52 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0348%, nfe)

Conditions

Monogenic short statue

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 17 of 20
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.5, phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0348% European (non-Finnish) · 406/1,167,286 alleles

Filtering AF 0.032% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0309%

Overall 0.0287% 457/1,592,634 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0504%	1,985
European (non-Finnish)grpmax	0.0348%	2,875
Admixed American	0.0135%	7,434
African / African-American	0.0107%	9,327
South Asian	0.00348%	28,713
East Asian	0.00226%	44,290

Remaining individuals 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.Arg798Ter
Coding: c.2392C>T
MANE Select: NM_032043
dbSNP: rs137852986
Type: single nucleotide variant
Location: chr17:61716051 (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

Monogenic short statue

Also linked: gastric cancer breast cancer ovarian cancer esophageal atresia/tracheoesophageal fistula breast-ovarian cancer, familial, susceptibility to, 1 Fanconi anemia complementation group J hereditary neoplastic syndrome familial ovarian cancer hereditary breast carcinoma Fanconi anemia

Similar variants

BRIP1 p.Arg798Gln Uncertain significance ★★ ⚠ 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-arg798ter (accessed [today's date]).

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