Is BAP1 p.Glu406Val (c.1217A>T) pathogenic?

BAP1 p.Glu406Val (c.1217A>T) is classified Conflicting classifications of pathogenicity in BAP1 (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2025-03-04). AlphaMissense: likely benign (0.156); Ultra-rare (popmax 0.0312%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Glu406Val (c.1217A>T)?

BAP1 p.Glu406Val (c.1217A>T) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Glu406Val (c.1217A>T) in the general population?

BAP1 p.Glu406Val (c.1217A>T) is ultra-rare (popmax 0.0312%, eas) (gnomAD).

What do computational predictors say about BAP1 p.Glu406Val (c.1217A>T)?

AlphaMissense predicts likely benign (score 0.156) — an in-silico prediction, not a clinical call.

BAP1 p.Glu406Val

c.1217A>T · rs535695655 · VCV240043

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.156 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.156	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -8.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.40	donor gain · deltas
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Overall
CADD	25.7	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

Grpmax group 0.0312% East Asian · 14/44,892 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.00155% 25/1,614,224 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0312%	3,207
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)	0.000847%	118,004

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BAP1
Protein: p.Glu406Val
Coding: c.1217A>T
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs535695655
Type: single nucleotide variant
Location: chr3:52404486 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB

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.Glu406Gly Uncertain significance ★★ ⚠ same residue
BAP1 p.Glu406= Likely benign ★★ same residue
BAP1 p.Glu406Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 p.Glu406Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 p.Glu406Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 p.Glu406del Conflicting classifications of pathogenicity ★ same residue
BAP1 c.1117-1G>A Likely pathogenic ★★ same condition
BAP1 c.122+1G>A 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-glu406val (accessed [today's date]).

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