Is BAP1 p.Pro391fs (c.1169dup) pathogenic?

BAP1 p.Pro391fs (c.1169dup) is classified Pathogenic in BAP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-31). No gnomAD frequency available for this variant; Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Pro391fs (c.1169dup)?

BAP1 p.Pro391fs (c.1169dup) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Pro391fs (c.1169dup) in the general population?

BAP1 p.Pro391fs (c.1169dup) is no gnomAD frequency available for this variant (gnomAD).

BAP1 p.Pro391fs

c.1169dup · rs1578222261 · VCV818479

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 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 LoF-intolerant gene
NMD	predicted	premature termination codon in exon 12 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2	GERP -2.5

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.Pro391fs
Coding: c.1169dup
MANE Select: NM_004656
dbSNP: rs1578222261
Type: Duplication
Location: chr3:52404533 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 391: the 'disordered' region; a UniProt-annotated variant site (in tpds1)

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.Pro391Leu Uncertain significance ★★ ⚠ same residue
BAP1 p.Pro391Ser Uncertain significance ★★ ⚠ same residue
BAP1 p.Pro391Ala Uncertain significance ★ ⚠ same residue
BAP1 p.Pro391Arg Uncertain significance ★ ⚠ same residue
BAP1 p.Pro391= Likely benign ★ same residue
BAP1 p.Arg146fs Pathogenic ★★ same condition
BAP1 p.Asn504fs Pathogenic ★★ same condition
BAP1 p.Cys320fs 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-pro391fs (accessed [today's date]).

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