Is BAP1 p.Glu406del (c.1215GGA[1]) pathogenic?

BAP1 p.Glu406del (c.1215GGA[1]) is classified Conflicting classifications of pathogenicity in BAP1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-17). Very rare (popmax 0.00167%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Glu406del (c.1215GGA[1])?

BAP1 p.Glu406del (c.1215GGA[1]) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Glu406del (c.1215GGA[1]) in the general population?

BAP1 p.Glu406del (c.1215GGA[1]) is very rare (popmax 0.00167%, amr) (gnomAD).

BAP1 p.Glu406del

c.1215GGA[1] · rs768718216 · VCV489606

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

hereditary neoplastic 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 -12	GERP -3.5
Overall
CADD	17.64	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	(TCATCC)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,992 alleles

Overall 0.00131% 2/152,216 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,992
African / African-American	0.00133%	74,940

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.Glu406del
Coding: c.1215GGA[1]
MANE Select: NM_004656
dbSNP: rs768718216
Type: Microsatellite
Location: chr3:52404483 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 406: 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.Glu406Gly Uncertain significance ★★ ⚠ same residue
BAP1 p.Glu406= Likely benign ★★ same residue
BAP1 p.Glu406Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 p.Glu406Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 p.Glu406Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 p.Glu406Val Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 p.Gln267fs Pathogenic ★★ same condition
BAP1 p.Glu611fs 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-glu406del (accessed [today's date]).

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