Is BAP1 p.Asn349Asp (c.1045A>G) pathogenic?

BAP1 p.Asn349Asp (c.1045A>G) is classified Conflicting classifications of pathogenicity in BAP1 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-12-28). AlphaMissense: likely benign (0.1462); Very rare (popmax 0.0033%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Asn349Asp (c.1045A>G)?

BAP1 p.Asn349Asp (c.1045A>G) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Asn349Asp (c.1045A>G) in the general population?

BAP1 p.Asn349Asp (c.1045A>G) is very rare (popmax 0.0033%, nfe) (gnomAD).

What do computational predictors say about BAP1 p.Asn349Asp (c.1045A>G)?

AlphaMissense predicts likely benign (score 0.1462) — an in-silico prediction, not a clinical call.

BAP1 p.Asn349Asp

c.1045A>G · rs765742255 · VCV490766

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1462 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0033%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1462	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -6.01	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 6.2	GERP 1.8, phastCons 0.99
Overall
CADD	19.11	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 0.0033% European (non-Finnish) · 39/1,180,046 alleles

Filtering AF 0.00247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00217%

Overall 0.0026% 42/1,614,008 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0033%	30,258
Remaining individualsnot grpmax-eligible	0.0032%	31,242
African / African-American	0.00133%	74,926

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.Asn349Asp
Coding: c.1045A>G
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs765742255
Type: single nucleotide variant
Location: chr3:52405181 (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.Asn349Lys Uncertain significance ★★ ⚠ same residue
BAP1 p.Asn349= Likely benign ★★ same residue
BAP1 p.Asn349Ile Uncertain significance ★ ⚠ same residue
BAP1 p.Asn349Ser 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.122+5G>A 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-asn349asp (accessed [today's date]).

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