Is BAP1 p.Ser705Asn (c.2114G>A) pathogenic?

BAP1 p.Ser705Asn (c.2114G>A) is classified Conflicting classifications of pathogenicity in BAP1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-06-15). AlphaMissense: likely pathogenic (0.9546); Very rare (popmax 7e-05%); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Ser705Asn (c.2114G>A)?

BAP1 p.Ser705Asn (c.2114G>A) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Ser705Asn (c.2114G>A) in the general population?

BAP1 p.Ser705Asn (c.2114G>A) is very rare (popmax 7e-05%) (gnomAD).

What do computational predictors say about BAP1 p.Ser705Asn (c.2114G>A)?

AlphaMissense predicts likely pathogenic (score 0.9546) — an in-silico prediction, not a clinical call.

BAP1 p.Ser705Asn

c.2114G>A · rs1704984916 · VCV2783918

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9546 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 7e-05%)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9546	likely pathogenic
REVEL	0.275	benign-leaning
SaProt	LLR -7.06	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Overall
CADD	25.0	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

Grpmax group 7e-05%

Overall 7e-05% 1/1,428,160 alleles · very rare

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.Ser705Asn
Coding: c.2114G>A
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs1704984916
Type: single nucleotide variant
Location: chr3:52402364 (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.Ser705= Likely benign ★★ same residue
BAP1 p.Ser705Arg Uncertain significance ★ ⚠ same residue
BAP1 p.Ser705Gly Uncertain significance ★ same residue
BAP1 p.Ser705Thr 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-ser705asn (accessed [today's date]).

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