Is BRIP1 p.Ser495fs (c.1483del) pathogenic?

BRIP1 p.Ser495fs (c.1483del) is classified Pathogenic in BRIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-04). No allele count reported in gnomAD v4.1 (AN 1,612,782); Associated with hereditary neoplastic syndrome.

What condition is associated with BRIP1 p.Ser495fs (c.1483del)?

BRIP1 p.Ser495fs (c.1483del) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BRIP1 p.Ser495fs (c.1483del) in the general population?

BRIP1 p.Ser495fs (c.1483del) is no allele count reported in gnomAD v4.1 (AN 1,612,782) (gnomAD).

BRIP1 p.Ser495fs

c.1483del · rs1555603622 · VCV3228090

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,782)

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 11 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.5	GERP 1.3, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,612,782). 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.Ser495fs
Coding: c.1483del
MANE Select: NM_032043
dbSNP: rs1555603622
Type: Deletion
Location: chr17:61784415 (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

Similar variants

BRIP1 p.Ser495Pro Uncertain significance ★★ same residue
BRIP1 p.Ser495Tyr Uncertain significance ★★ ⚠ same residue
BRIP1 p.Ser495= Benign/Likely benign ★★ same residue
BRIP1 p.Ser495Phe Uncertain significance ★ ⚠ same residue
BRIP1 p.Ser495Thr Uncertain significance ★ ⚠ same residue
BRIP1 c.1629-3_1634del Likely pathogenic ★★ same condition
BRIP1 c.1936del Pathogenic ★★ same condition
BRIP1 c.205+1del 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-ser495fs (accessed [today's date]).

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