Is BRIP1 p.Arg162Ter (c.484C>T) pathogenic?

BRIP1 p.Arg162Ter (c.484C>T) is classified Pathogenic/Likely pathogenic in BRIP1 (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-01-21). Ultra-rare (popmax 0.0165%, mid); Associated with BRIP1-related disorder.

What condition is associated with BRIP1 p.Arg162Ter (c.484C>T)?

BRIP1 p.Arg162Ter (c.484C>T) is associated with BRIP1-related disorder, gastric cancer, hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRIP1 p.Arg162Ter (c.484C>T) in the general population?

BRIP1 p.Arg162Ter (c.484C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

BRIP1 p.Arg162Ter

c.484C>T · rs747604569 · VCV186411

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

BRIP1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 5 of 20
Splicing
SpliceAI	Δ0.51	donor loss, 23 bp away · masked 0 · deltas
Pangolin	Δ0.54	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.6	GERP 1.4, phastCons 1
Overall
CADD	36.0	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 0.0165% Middle Eastern · 1/6,078 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00105% 17/1,613,260 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,078
African / African-American	0.00535%	18,709
Finnishnot grpmax-eligible	0.00313%	31,986
Remaining individualsnot grpmax-eligible	0.0016%	62,454
South Asian	0.0011%	91,050
European (non-Finnish)	0.000678%	147,451

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.Arg162Ter
Coding: c.484C>T
MANE Select: NM_032043
dbSNP: rs747604569
Type: single nucleotide variant
Location: chr17:61849152 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 162: the helicase atp-binding domain

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

Disease context

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

Similar variants

BRIP1 p.Arg162Pro Uncertain significance ★★ ⚠ same residue
BRIP1 p.Arg162Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
BRIP1 p.Arg162Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
BRIP1 p.Arg162= Likely benign ★ 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-arg162ter (accessed [today's date]).

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