Is BRIP1 p.Ile562Val (c.1684A>G) pathogenic?

BRIP1 p.Ile562Val (c.1684A>G) is classified Conflicting classifications of pathogenicity in BRIP1 (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-05-22). AlphaMissense: likely benign (0.0637); Very rare (popmax 0.00288%, nfe); Associated with familial ovarian cancer.

What condition is associated with BRIP1 p.Ile562Val (c.1684A>G)?

BRIP1 p.Ile562Val (c.1684A>G) is associated with familial ovarian cancer, ovarian cancer, Fanconi anemia complementation group J (ClinVar).

How common is BRIP1 p.Ile562Val (c.1684A>G) in the general population?

BRIP1 p.Ile562Val (c.1684A>G) is very rare (popmax 0.00288%, nfe) (gnomAD).

What do computational predictors say about BRIP1 p.Ile562Val (c.1684A>G)?

AlphaMissense predicts likely benign (score 0.0637) — an in-silico prediction, not a clinical call.

BRIP1 p.Ile562Val

c.1684A>G · rs45533636 · VCV182352

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.0637 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00288%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial ovarian cancer

Computational evidence

Protein change
AlphaMissense	0.0637	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -5.31	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 -0.15	GERP 0.93
Regional constraint	o/e 0.84	unconstrained · MANE · 110 kb · p 3.3e-06 · regional, not allelic
Overall
CADD	1.322	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 0.00288% European (non-Finnish) · 34/1,180,018 alleles

Filtering AF 0.00207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00223% 36/1,613,980 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00288%	34,706
Remaining individualsnot grpmax-eligible	0.0016%	62,490
African / African-American	0.00133%	74,920

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.Ile562Val
Coding: c.1684A>G
MANE Select: NM_032043
dbSNP: rs45533636
Type: single nucleotide variant
Location: chr17:61780950 (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

familial ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

BRIP1 p.Ile562Met Uncertain significance ★★ ⚠ same residue
BRIP1 p.Ile562= Likely benign ★★ same residue
BRIP1 p.Ile562Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
BRIP1 p.Ile562fs 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-ile562val (accessed [today's date]).

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