Is BRIP1 p.Ser215fs (c.643_644insGTGGCACCCC) pathogenic?

BRIP1 p.Ser215fs (c.643644insGTGGCACCCC) is classified Pathogenic in BRIP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-20). Absent from gnomAD; Associated with Fanconi anemia complementation group J.

What condition is associated with BRIP1 p.Ser215fs (c.643_644insGTGGCACCCC)?

BRIP1 p.Ser215fs (c.643_644insGTGGCACCCC) is associated with Fanconi anemia complementation group J, hereditary breast carcinoma (ClinVar).

How common is BRIP1 p.Ser215fs (c.643_644insGTGGCACCCC) in the general population?

BRIP1 p.Ser215fs (c.643_644insGTGGCACCCC) is absent from gnomAD (gnomAD).

BRIP1 p.Ser215fs

c.643_644insGTGGCACCCC · rs2545200773 · VCV2121737

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Fanconi anemia complementation group J

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 7 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP 1.6, phastCons 0.93

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BRIP1
Protein: p.Ser215fs
Coding: c.643_644insGTGGCACCCC
MANE Select: NM_032043
dbSNP: rs2545200773
Type: Insertion
Location: chr17:61808741 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 215: the helicase atp-binding domain

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: hereditary breast carcinoma

Similar variants

BRIP1 p.Ser215Cys Uncertain significance ★★ ⚠ same residue
BRIP1 p.Ser215Phe Uncertain significance ★★ ⚠ same residue
BRIP1 p.Ser215Tyr Uncertain significance ★★ ⚠ same residue
BRIP1 p.Ser215= Conflicting classifications of pathogenicity ★ same residue
BRIP1 p.Ser215Pro Uncertain significance ★ ⚠ same residue
BRIP1 p.Asp566_Lys567insIleSerAsnTer Pathogenic ★★ same condition
BRIP1 p.Leu340fs Pathogenic/Likely pathogenic ★★ same condition
BRIP1 p.Pro619fs 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-ser215fs (accessed [today's date]).

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