Is BAP1 p.Ala378Leu (c.1132_1133delinsTT) pathogenic?

BAP1 p.Ala378Leu (c.11321133delinsTT) is classified Uncertain significance in BAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-05). No gnomAD frequency available for this variant; Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Ala378Leu (c.1132_1133delinsTT)?

BAP1 p.Ala378Leu (c.1132_1133delinsTT) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Ala378Leu (c.1132_1133delinsTT) in the general population?

BAP1 p.Ala378Leu (c.1132_1133delinsTT) is no gnomAD frequency available for this variant (gnomAD).

BAP1 p.Ala378Leu

c.1132_1133delinsTT · rs2471333652 · VCV2774755

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Ala378Leu
Coding: c.1132_1133delinsTT
MANE Select: NM_004656
dbSNP: rs2471333652
Type: Indel
Location: chr3:52404570 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 378: 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

Also linked: BAP1-related tumor predisposition syndrome

Similar variants

BAP1 p.Ala378Thr Uncertain significance ★★ ⚠ same residue
BAP1 p.Ala378Val Uncertain significance ★★ ⚠ same residue
BAP1 p.Ala378= Likely benign ★ same residue
BAP1 p.Ala304Asn Uncertain significance ★★ same condition
BAP1 p.Ala471Ile Uncertain significance ★★ same condition
BAP1 p.Glu198Leu Uncertain significance ★★ same condition
BAP1 c.249_255+15delinsAGACC Likely pathogenic ★ same condition
BAP1 c.375_375+3delinsACC 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-ala378leu (accessed [today's date]).

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