Is BAP1 p.Val616= (c.1848G>A) pathogenic?

BAP1 p.Val616= (c.1848G>A) is classified Uncertain significance in BAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-26). Very rare (popmax 0.0011%, sas); Associated with BAP1-related tumor predisposition syndrome.

What condition is associated with BAP1 p.Val616= (c.1848G>A)?

BAP1 p.Val616= (c.1848G>A) is associated with BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Val616= (c.1848G>A) in the general population?

BAP1 p.Val616= (c.1848G>A) is very rare (popmax 0.0011%, sas) (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.Val616=

c.1848G>A · rs757559034 · VCV2010737

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

BAP1-related tumor predisposition 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
Pangolin	Δ0.68	gain · loss 0.40 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 1.6	GERP -3.5, phastCons 0.98
Overall
CADD	17.65	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,080 alleles

Overall 6.2e-05% 1/1,614,158 alleles · very rare exomes 1/1,461,802 · genomes 0/152,356 · joint denominator

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.Val616=
Coding: c.1848G>A
MANE Select: NM_004656
dbSNP: rs757559034
Type: single nucleotide variant
Location: chr3:52403180 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 616: a UniProt-annotated variant site (in tpds1); a UniProt-annotated variant site (in); the 'disordered' region; the 'interaction with brca1' region

Full BAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

BAP1-related tumor predisposition syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For BAP1-related tumor predisposition syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

BAP1 p.Val616Met Uncertain significance ★ ⚠ same residue
BAP1 p.Val616Ala Uncertain significance ★ ⚠ same residue
BAP1 p.Val616Gly 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
BAP1 c.122+5G>C 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-val616 (accessed [today's date]).

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