Is BAP1 p.Asp199Glu (c.597C>A) pathogenic?

BAP1 p.Asp199Glu (c.597C>A) is classified Uncertain significance in BAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-14). AlphaMissense: likely benign (0.0997); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Asp199Glu (c.597C>A)?

BAP1 p.Asp199Glu (c.597C>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Asp199Glu (c.597C>A) in the general population?

BAP1 p.Asp199Glu (c.597C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BAP1 p.Asp199Glu (c.597C>A)?

AlphaMissense predicts likely benign (score 0.0997) — an in-silico prediction, not a clinical call.

BAP1 p.Asp199Glu

c.597C>A · VCV4867364

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0997 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,571,528)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0997	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -6.87	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 1.7	GERP 0.07, phastCons 1
Overall
CADD	11.77	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

No allele count reported in gnomAD v4.1 (AN 1,571,528). 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.Asp199Glu
Coding: c.597C>A
MANE Select: NM_007212 · reported on NM_004656
Type: single nucleotide variant
Location: chr3:52406891 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB
Residue 199: the 'disordered' region

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.Asp199= Benign/Likely benign ★★ same residue
BAP1 p.Asp199Asn Uncertain significance ★ ⚠ same residue
RNF2 p.Thr199Ala 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

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-asp199glu (accessed [today's date]).

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