Is BAP1 p.Pro339= (c.1017A>G) pathogenic?

BAP1 p.Pro339= (c.1017A>G) is classified Likely benign in BAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-02-08). Very rare (popmax 0.00133%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Pro339= (c.1017A>G)?

BAP1 p.Pro339= (c.1017A>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Pro339= (c.1017A>G) in the general population?

BAP1 p.Pro339= (c.1017A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

BAP1 p.Pro339=

c.1017A>G · rs779774919 · VCV631327

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.1	GERP -3.5, phastCons 0.98
Overall
CADD	6.038	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,056 alleles

Overall 0.000124% 2/1,614,106 alleles · very rare exomes 2/1,461,792 · genomes 0/152,314 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,056
European (non-Finnish)	8.47e-05%	1,180,026

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.Pro339=
Coding: c.1017A>G
MANE Select: NM_004656
dbSNP: rs779774919
Type: single nucleotide variant
Location: chr3:52405209 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 339: 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

Similar variants

BAP1 p.Pro339Ala Uncertain significance ★ ⚠ same residue
BAP1 p.Pro339Leu 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.1251-1G>A Likely pathogenic ★★ same condition
BAP1 c.1251-2A>G Likely pathogenic ★★ same condition
BAP1 c.1729+1G>A 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-pro339 (accessed [today's date]).

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