Is BAP1 p.Lys656fs (c.1966_1967del) pathogenic?

BAP1 p.Lys656fs (c.19661967del) is classified Pathogenic in BAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-21). Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Lys656fs (c.1966_1967del)?

BAP1 p.Lys656fs (c.1966_1967del) is associated with hereditary neoplastic syndrome (ClinVar).

BAP1 p.Lys656fs

c.1966_1967del · VCV3260394

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 15 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.2	GERP 0.91, phastCons 1

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

Variant & gene context

Gene: BAP1
Protein: p.Lys656fs
Coding: c.1966_1967del
MANE Select: NM_004656
Type: Deletion
Location: chr3:52402795 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 656: an α-helix; a UniProt-annotated variant site (in tpds1); the 'interaction with brca1' region; the 'interaction with yy1' 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

Similar variants

BAP1 p.Lys656= Benign/Likely benign ★★ same residue
BAP1 c.123-10_129del Likely pathogenic ★★ same condition
BAP1 c.1729+1del Pathogenic ★★ same condition
BAP1 c.659+1del Likely pathogenic ★★ same condition
BAP1 p.Ala138fs Pathogenic ★★ same condition
BAP1 p.Arg207fs Pathogenic ★★ same condition
BAP1 p.Arg518fs Pathogenic ★★ same condition
BAP1 p.Asn363fs 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-lys656fs (accessed [today's date]).

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