Is BAP1 p.Met80fs (c.238_239del) pathogenic?

BAP1 p.Met80fs (c.238239del) is classified Pathogenic in BAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-06). Very rare (popmax 8.48e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Met80fs (c.238_239del)?

BAP1 p.Met80fs (c.238_239del) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Met80fs (c.238_239del) in the general population?

BAP1 p.Met80fs (c.238_239del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

BAP1 p.Met80fs

c.238_239del · rs1705235390 · VCV965729

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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 haploinsufficient gene (ClinGen); NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,096 alleles

Overall 6.85e-05% 1/1,459,538 alleles · very rare

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.Met80fs
Coding: c.238_239del
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs1705235390
Type: Deletion
Location: chr3:52408490 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB
Residue 80: the 'interaction with hip2' region; an α-helix

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.Met80Ile Uncertain significance ★★ ⚠ same residue
BAP1 p.Met80Val Uncertain significance ★★ ⚠ same residue
BAP1 p.Met80Thr 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
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-met80fs (accessed [today's date]).

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