Is BAP1 p.Asn504Ser (c.1511A>G) pathogenic?

BAP1 p.Asn504Ser (c.1511A>G) is classified Conflicting classifications of pathogenicity in BAP1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-02). AlphaMissense: ambiguous (0.5346); Very rare (popmax 0.00333%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Asn504Ser (c.1511A>G)?

BAP1 p.Asn504Ser (c.1511A>G) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Asn504Ser (c.1511A>G) in the general population?

BAP1 p.Asn504Ser (c.1511A>G) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about BAP1 p.Asn504Ser (c.1511A>G)?

AlphaMissense predicts ambiguous (score 0.5346) — an in-silico prediction, not a clinical call.

BAP1 p.Asn504Ser

c.1511A>G · rs776634869 · VCV1774209

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5346 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.5346	ambiguous
REVEL	0.163	moderately benign-leaning
SaProt	LLR -4.64	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Overall
CADD	25.3	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

Grpmax group 0.00333% Admixed American · 2/59,996 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000205% 3/1,461,606 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,998
European (non-Finnish)	8.48e-05%	1,179,788

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.Asn504Ser
Coding: c.1511A>G
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs776634869
Type: single nucleotide variant
Location: chr3:52403634 (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.Asn504Lys Uncertain significance ★★ ⚠ same residue
BAP1 p.Asn504His Uncertain significance ★ ⚠ same residue
BAP1 p.Asn504Thr Uncertain significance ★ ⚠ same residue
BAP1 p.Asn504fs Pathogenic ★★ 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-asn504ser (accessed [today's date]).

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