Is BRIP1 p.Ser53Ile (c.158_159delinsTT) pathogenic?

BRIP1 p.Ser53Ile (c.158159delinsTT) is classified Uncertain significance in BRIP1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-18). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with BRIP1 p.Ser53Ile (c.158_159delinsTT)?

BRIP1 p.Ser53Ile (c.158_159delinsTT) is associated with hereditary neoplastic syndrome, Fanconi anemia complementation group J, hereditary breast carcinoma (ClinVar).

How common is BRIP1 p.Ser53Ile (c.158_159delinsTT) in the general population?

BRIP1 p.Ser53Ile (c.158_159delinsTT) is absent from gnomAD (gnomAD).

BRIP1 p.Ser53Ile

c.158_159delinsTT · rs786202417 · VCV185741

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.1	GERP -1.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 68 kb · p 0.065 · regional, not allelic

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.Ser53Ile
Coding: c.158_159delinsTT
MANE Select: NM_032043
dbSNP: rs786202417
Type: Indel
Location: chr17:61859842 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 53: 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: Fanconi anemia complementation group J hereditary breast carcinoma

Similar variants

BRIP1 p.Ser53fs Pathogenic ★★ same residue
BRIP1 p.Ser53Asn Uncertain significance ★★ ⚠ same residue
BRIP1 p.Ser53= Likely benign ★★ same residue
BRIP1 p.Ser53Thr Uncertain significance ★ ⚠ same residue
BRIP1 c.204_205+1delinsAGT Likely pathogenic ★★ same condition
BRIP1 c.2380-45_2402delinsTTGACCATTTGAATGGT Likely pathogenic ★★ same condition
BRIP1 c.2398_2400delinsATTTG Pathogenic/Likely pathogenic ★★ same condition
BRIP1 p.His715fs 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-ser53ile (accessed [today's date]).

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