Is BAP1 p.Glu693Lys (c.2077G>A) pathogenic?

BAP1 p.Glu693Lys (c.2077G>A) is classified Uncertain significance in BAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-21). AlphaMissense: likely pathogenic (0.9927); No allele count reported in gnomAD v4.1 (AN 1,568,178); Associated with BAP1-related tumor predisposition syndrome.

What condition is associated with BAP1 p.Glu693Lys (c.2077G>A)?

BAP1 p.Glu693Lys (c.2077G>A) is associated with BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Glu693Lys (c.2077G>A) in the general population?

BAP1 p.Glu693Lys (c.2077G>A) is no allele count reported in gnomAD v4.1 (AN 1,568,178) (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.Glu693Lys (c.2077G>A)?

AlphaMissense predicts likely pathogenic (score 0.9927) — an in-silico prediction, not a clinical call.

BAP1 p.Glu693Lys

c.2077G>A · VCV3654063

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9927 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,568,178)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

BAP1-related tumor predisposition syndrome

Computational evidence

Protein change
AlphaMissense	0.9927	likely pathogenic
REVEL	0.357	indeterminate
SaProt	LLR -7.75	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,568,178). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BAP1
Protein: p.Glu693Lys
Coding: c.2077G>A
MANE Select: NM_004656
Type: single nucleotide variant
Location: chr3:52402401 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 693: an α-helix; the uld domain; a UniProt-annotated variant site (in tpds1); 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.Glu693= Benign/Likely benign ★★ same residue
BAP1 p.Glu693Val 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
BAP1 c.1251-1G>A 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-glu693lys (accessed [today's date]).

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