Is BAP1 p.Asn690= (c.2070C>T) pathogenic?

BAP1 p.Asn690= (c.2070C>T) is classified Likely benign in BAP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-06-02). Very rare (popmax 6.38e-05%); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Asn690= (c.2070C>T)?

BAP1 p.Asn690= (c.2070C>T) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Asn690= (c.2070C>T) in the general population?

BAP1 p.Asn690= (c.2070C>T) is very rare (popmax 6.38e-05%) (gnomAD).

BAP1 p.Asn690=

c.2070C>T · rs1553644559 · VCV539937

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 6.38e-05%)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.111	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP -0.3, phastCons 1
Overall
CADD	7.046	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.38e-05%

Overall 6.38e-05% 1/1,567,952 alleles · very rare exomes 1/1,415,630 · genomes 0/152,322 · joint denominator

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.Asn690=
Coding: c.2070C>T
MANE Select: NM_004656
dbSNP: rs1553644559
Type: single nucleotide variant
Location: chr3:52402408 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 690: an α-helix; the uld domain; a UniProt-annotated variant site (in tpds1); the 'interaction with brca1' region

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.Asn690Ser Uncertain significance ★★ ⚠ same residue
BAP1 p.Asn690Asp Uncertain significance ★ ⚠ same residue
BAP1 p.Asn690Lys 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
BAP1 c.122+5G>C 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-asn690 (accessed [today's date]).

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