Is BAP1 p.Leu17fs (c.49dup) pathogenic?

BAP1 p.Leu17fs (c.49dup) is classified Pathogenic in BAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-15). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Leu17fs (c.49dup)?

BAP1 p.Leu17fs (c.49dup) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Leu17fs (c.49dup) in the general population?

BAP1 p.Leu17fs (c.49dup) is absent from gnomAD (gnomAD).

BAP1 p.Leu17fs

c.49dup · rs2153228628 · VCV1417901

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

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-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1

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: BAP1
Protein: p.Leu17fs
Coding: c.49dup
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs2153228628
Type: Duplication
Location: chr3:52409731 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB
Residue 17: the 'interaction with hip2' region

Full BAP1 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: BAP1-related tumor predisposition syndrome

Similar variants

BAP1 p.Leu17= Likely benign ★★ same residue
BAP1 p.Leu17Pro Uncertain significance ★ ⚠ same residue
BAP1 p.Arg146fs Pathogenic ★★ same condition
BAP1 p.Asn504fs Pathogenic ★★ same condition
BAP1 p.Cys320fs Pathogenic ★★ same condition
BAP1 p.Gln253fs Pathogenic ★★ same condition
BAP1 p.Gln280fs Pathogenic ★★ same condition
BAP1 p.Glu198fs 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/bap1-p-leu17fs (accessed [today's date]).

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