Is BRIP1 p.Ala551fs (c.1645_1649dup) pathogenic?

BRIP1 p.Ala551fs (c.16451649dup) is classified Pathogenic in BRIP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-29). Ultra-rare (gnomAD MAF 7.136e-07); Associated with hereditary neoplastic syndrome.

What condition is associated with BRIP1 p.Ala551fs (c.1645_1649dup)?

BRIP1 p.Ala551fs (c.1645_1649dup) is associated with hereditary neoplastic syndrome, Fanconi anemia complementation group J, hereditary breast carcinoma (ClinVar).

How common is BRIP1 p.Ala551fs (c.1645_1649dup) in the general population?

BRIP1 p.Ala551fs (c.1645_1649dup) is ultra-rare (gnomAD MAF 7.136e-07) (gnomAD).

BRIP1 p.Ala551fs

c.1645_1649dup · rs1555602638 · VCV479418

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 7.136e-07)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 12 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP -4.5, phastCons 1

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

Population frequency

dbSNP / gnomAD

Global frequency 7.14e-05% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: BRIP1
Protein: p.Ala551fs
Coding: c.1645_1649dup
MANE Select: NM_032043
dbSNP: rs1555602638
Type: Duplication
Location: chr17:61780984 (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

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

Also linked: Fanconi anemia complementation group J hereditary breast carcinoma

Similar variants

BRIP1 p.Ala551Glu Uncertain significance ★★ ⚠ same residue
BRIP1 p.Ala551Thr Uncertain significance ★★ ⚠ same residue
BRIP1 p.Ala551Val Uncertain significance ★★ ⚠ same residue
BRIP1 p.Ala551= Benign/Likely benign ★★ same residue
BRIP1 p.Ala551Gly Uncertain significance ★ ⚠ same residue
BRIP1 p.Ala551Pro Uncertain significance ★ ⚠ same residue
BRIP1 c.2492+2dup Pathogenic/Likely pathogenic ★★ same condition
BRIP1 p.Ala27fs 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-ala551fs (accessed [today's date]).

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