Is BAP1 p.Arg146Thr (c.437G>C) pathogenic?

BAP1 p.Arg146Thr (c.437G>C) is classified Likely pathogenic in BAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-26). AlphaMissense: likely pathogenic (0.9905); Absent from gnomAD v4.1; Associated with astrocytoma (excluding glioblastoma).

What condition is associated with BAP1 p.Arg146Thr (c.437G>C)?

BAP1 p.Arg146Thr (c.437G>C) is associated with astrocytoma (excluding glioblastoma), hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Arg146Thr (c.437G>C) in the general population?

BAP1 p.Arg146Thr (c.437G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BAP1 p.Arg146Thr (c.437G>C)?

AlphaMissense predicts likely pathogenic (score 0.9905) — an in-silico prediction, not a clinical call.

BAP1 p.Arg146Thr

c.437G>C · rs1705201387 · VCV1698836

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9905 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

astrocytoma (excluding glioblastoma)

Computational evidence

Protein change
AlphaMissense	0.9905	likely pathogenic ✓ concordant with ClinVar
REVEL	0.174	moderately benign-leaning
SaProt	LLR -12.07	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	Δ0.85	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.79	loss · gain 0.04 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Overall
CADD	33.0	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

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.Arg146Thr
Coding: c.437G>C
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs1705201387
Type: single nucleotide variant
Location: chr3:52407399 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB
Residue 146: the 'interaction with hip2' region

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

Disease context

astrocytoma (excluding glioblastoma) — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

Similar variants

BAP1 p.Arg146Gly Uncertain significance ★★ ⚠ same residue
BAP1 p.Arg146= Likely benign ★ same residue
BAP1 p.Arg146fs Pathogenic ★★ same residue
BAP1 p.Arg146Lys 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

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-arg146thr (accessed [today's date]).

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