Is BAP1 p.Phe22fs (c.65del) pathogenic?

BAP1 p.Phe22fs (c.65del) is classified Pathogenic in BAP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-22). Absent from gnomAD; Associated with BAP1-related tumor predisposition syndrome.

What condition is associated with BAP1 p.Phe22fs (c.65del)?

BAP1 p.Phe22fs (c.65del) is associated with BAP1-related tumor predisposition syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Phe22fs (c.65del) in the general population?

BAP1 p.Phe22fs (c.65del) is absent from gnomAD (gnomAD).

How is BAP1-related tumor predisposition syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

BAP1 p.Phe22fs

c.65del · rs1060503735 · VCV412414

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

BAP1-related tumor predisposition 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 2.1	GERP -2.9, 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.Phe22fs
Coding: c.65del
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs1060503735
Type: Deletion
Location: chr3:52409716 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB
Residue 22: the 'interaction with hip2' region; an α-helix

Full BAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Also linked: hereditary neoplastic syndrome

For BAP1-related tumor predisposition syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

BAP1 p.Phe22Ile Uncertain significance ★★ ⚠ same residue
BAP1 p.Phe22Ter Pathogenic ★ same residue
BAP1 p.Phe22= Conflicting classifications of pathogenicity ★ same residue
BAP1 p.Phe22Cys Uncertain significance ★ ⚠ same residue
BAP1 c.123-10_129del Likely pathogenic ★★ same condition
BAP1 c.1729+1del Pathogenic ★★ same condition
BAP1 c.1984-3_1999del Likely pathogenic ★★ same condition
BAP1 c.659+1del 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-phe22fs (accessed [today's date]).

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