Is BAP1 p.Lys651del (c.1951_1953del) pathogenic?

BAP1 p.Lys651del (c.19511953del) is classified Uncertain significance in BAP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-09-27). Very rare (popmax 0.00133%, afr); Associated with BAP1-related tumor predisposition syndrome.

What condition is associated with BAP1 p.Lys651del (c.1951_1953del)?

BAP1 p.Lys651del (c.1951_1953del) is associated with BAP1-related tumor predisposition syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Lys651del (c.1951_1953del) in the general population?

BAP1 p.Lys651del (c.1951_1953del) is very rare (popmax 0.00133%, afr) (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.Lys651del

c.1951_1953del · rs1226165465 · VCV485250

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

BAP1-related tumor predisposition syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Overall
CADD	17.39	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,932 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,614,114 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,932
European (non-Finnish)	0.000254%	393,349

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BAP1
Protein: p.Lys651del
Coding: c.1951_1953del
MANE Select: NM_004656
dbSNP: rs1226165465
Type: Deletion
Location: chr3:52402809 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 651: 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

Also linked: hereditary neoplastic syndrome

For BAP1-related tumor predisposition syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

BAP1 p.Lys651Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 p.Lys651Asn Uncertain significance ★ ⚠ same residue
BAP1 p.Lys651= Likely benign ★ 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
BAP1 p.Ala138fs 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-lys651del (accessed [today's date]).

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