Is BRIP1 p.Arg162Leu (c.485G>T) pathogenic?

BRIP1 p.Arg162Leu (c.485G>T) is classified Conflicting classifications of pathogenicity in BRIP1 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2025-07-16). AlphaMissense: ambiguous (0.373); Very rare (popmax 0.00534%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BRIP1 p.Arg162Leu (c.485G>T)?

BRIP1 p.Arg162Leu (c.485G>T) is associated with hereditary neoplastic syndrome, ovarian cancer, Fanconi anemia complementation group J (ClinVar).

How common is BRIP1 p.Arg162Leu (c.485G>T) in the general population?

BRIP1 p.Arg162Leu (c.485G>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about BRIP1 p.Arg162Leu (c.485G>T)?

AlphaMissense predicts ambiguous (score 0.373) — an in-silico prediction, not a clinical call.

BRIP1 p.Arg162Leu

c.485G>T · rs61757643 · VCV142492

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

ambiguous

0.373 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.373	ambiguous
REVEL	0.267	benign-leaning
SaProt	LLR -6.07	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.29	donor loss, 22 bp away · masked 0 · deltas
Pangolin	Δ0.32	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 68 kb · p 0.065 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,962 alleles

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

Overall 0.00031% 5/1,613,424 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,740
Remaining individualsnot grpmax-eligible	0.0016%	62,474

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.Arg162Leu
Coding: c.485G>T
MANE Select: NM_032043
dbSNP: rs61757643
Type: single nucleotide variant
Location: chr17:61849151 (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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

BRIP1 p.Arg162Ter Pathogenic/Likely pathogenic ★★ same residue
BRIP1 p.Arg162Pro Uncertain significance ★★ ⚠ same residue
BRIP1 p.Arg162Gln 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-arg162leu (accessed [today's date]).

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