Is BAP1 p.Val171fs (c.510dup) pathogenic?

BAP1 p.Val171fs (c.510dup) is classified Pathogenic in BAP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-20). Very rare (popmax 0.000169%, nfe); Associated with BAP1-related tumor predisposition syndrome.

What condition is associated with BAP1 p.Val171fs (c.510dup)?

BAP1 p.Val171fs (c.510dup) is associated with BAP1-related tumor predisposition syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Val171fs (c.510dup) in the general population?

BAP1 p.Val171fs (c.510dup) is very rare (popmax 0.000169%, nfe) (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.Val171fs

c.510dup · rs1553645809 · VCV412430

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

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 7.7	GERP 1.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,024 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,882 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.Val171fs
Coding: c.510dup
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs1553645809
Type: Duplication
Location: chr3:52407243 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB
Residue 171: the 'interaction with hip2' region; the 'disordered' 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.Arg146fs Pathogenic ★★ same condition
BAP1 p.Asn504fs Pathogenic ★★ same condition
BAP1 p.Cys320fs Pathogenic ★★ same condition
BAP1 p.Gln253fs Pathogenic ★★ same condition
BAP1 p.Gln280fs Pathogenic ★★ same condition
BAP1 p.Glu198fs Pathogenic/Likely pathogenic ★★ same condition
BAP1 p.Glu454fs Pathogenic/Likely pathogenic ★★ same condition
BAP1 p.Glu566Ter 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-val171fs (accessed [today's date]).

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