Is BAP1 p.Pro268Leu (c.803C>T) pathogenic?

BAP1 p.Pro268Leu (c.803C>T) is classified Uncertain significance in BAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-10). AlphaMissense: likely pathogenic (0.8186); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Pro268Leu (c.803C>T)?

BAP1 p.Pro268Leu (c.803C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Pro268Leu (c.803C>T) in the general population?

BAP1 p.Pro268Leu (c.803C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BAP1 p.Pro268Leu (c.803C>T)?

AlphaMissense predicts likely pathogenic (score 0.8186) — an in-silico prediction, not a clinical call.

BAP1 p.Pro268Leu

c.803C>T · VCV3260364

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8186 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.8186	likely pathogenic
REVEL	0.145	moderately benign-leaning
SaProt	LLR -13.27	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Overall
CADD	26.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BAP1
Protein: p.Pro268Leu
Coding: c.803C>T
MANE Select: NM_007212 · reported on NM_004656
Type: single nucleotide variant
Location: chr3:52405893 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB
Residue 268: an α-helix

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.Pro268Ser 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
BAP1 c.1730-2A>G 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-pro268leu (accessed [today's date]).

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