Is BRIP1 p.Arg106Cys (c.316C>T) pathogenic?

BRIP1 p.Arg106Cys (c.316C>T) is classified Conflicting classifications of pathogenicity in BRIP1 (ClinVar, Conflicting submitters, 19 submitters; last evaluated 2026-01-31). AlphaMissense: likely benign (0.0666); Ultra-rare (popmax 0.0183%, amr); Associated with Fanconi anemia complementation group J.

What condition is associated with BRIP1 p.Arg106Cys (c.316C>T)?

BRIP1 p.Arg106Cys (c.316C>T) is associated with Fanconi anemia complementation group J, ovarian cancer, hereditary neoplastic syndrome (ClinVar).

How common is BRIP1 p.Arg106Cys (c.316C>T) in the general population?

BRIP1 p.Arg106Cys (c.316C>T) is ultra-rare (popmax 0.0183%, amr) (gnomAD).

What do computational predictors say about BRIP1 p.Arg106Cys (c.316C>T)?

AlphaMissense predicts likely benign (score 0.0666) — an in-silico prediction, not a clinical call.

BRIP1 p.Arg106Cys

c.316C>T · rs587780247 · VCV128184

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 19 submitters

AlphaMissense

likely benign

0.0666 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Fanconi anemia complementation group J

Computational evidence

Protein change
AlphaMissense	0.0666	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -6.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -0.42, phastCons 0.008
Regional constraint	o/e 0.92	unconstrained · MANE · 68 kb · p 0.065 · regional, not allelic
Overall
CADD	18.84	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 0.0183% Admixed American · 11/59,992 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00785%

Overall 0.00675% 109/1,613,894 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0183%	5,454
European (non-Finnish)	0.00746%	13,408
South Asian	0.00549%	18,216
Remaining individualsnot grpmax-eligible	0.0048%	20,827
African / African-American	0.00267%	37,459

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.Arg106Cys
Coding: c.316C>T
MANE Select: NM_032043
dbSNP: rs587780247
Type: single nucleotide variant
Location: chr17:61857121 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 106: the helicase atp-binding domain; the 'disordered' region

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

Disease context

Fanconi anemia complementation group J — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ovarian cancer hereditary neoplastic syndrome familial ovarian cancer hereditary breast carcinoma ovarian neoplasm

Similar variants

BRIP1 p.Arg106Ser Uncertain significance ★★ ⚠ same residue
BRIP1 p.Arg106= Benign/Likely benign ★★ same residue
BRIP1 p.Arg106His Conflicting classifications of pathogenicity ★ ⚠ 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
BRIP1 c.1340+1G>A Pathogenic/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-arg106cys (accessed [today's date]).

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