Is BAP1 p.Leu343Val (c.1027C>G) pathogenic?

BAP1 p.Leu343Val (c.1027C>G) is classified Uncertain significance in BAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-01). AlphaMissense: likely benign (0.0623); Very rare (popmax 8.47e-05%, nfe); Associated with BAP1-related tumor predisposition syndrome.

What condition is associated with BAP1 p.Leu343Val (c.1027C>G)?

BAP1 p.Leu343Val (c.1027C>G) is associated with BAP1-related tumor predisposition syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Leu343Val (c.1027C>G) in the general population?

BAP1 p.Leu343Val (c.1027C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is BAP1-related tumor predisposition syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about BAP1 p.Leu343Val (c.1027C>G)?

AlphaMissense predicts likely benign (score 0.0623) — an in-silico prediction, not a clinical call.

BAP1 p.Leu343Val

c.1027C>G · rs1060503734 · VCV412413

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0623 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BAP1-related tumor predisposition syndrome

Computational evidence

Protein change
AlphaMissense	0.0623	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -5.68	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 0.66, phastCons 1
Overall
CADD	17.63	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,036 alleles

Overall 6.84e-05% 1/1,461,802 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.Leu343Val
Coding: c.1027C>G
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs1060503734
Type: single nucleotide variant
Location: chr3:52405199 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB

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.Leu343Phe Uncertain significance ★★ ⚠ same residue
BAP1 p.Leu343Pro Uncertain significance ★★ ⚠ same residue
BAP1 p.Leu343= Benign/Likely benign ★★ same residue
BAP1 p.Leu343Arg Uncertain significance ★ ⚠ same residue
BAP1 c.1117-1G>A Likely pathogenic ★★ same condition
BAP1 c.122+1G>A Pathogenic ★★ same condition
BAP1 c.122+1G>T Pathogenic/Likely pathogenic ★★ same condition
BAP1 c.122+5G>A Pathogenic/Likely 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-leu343val (accessed [today's date]).

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