Is BAP1 p.Arg718Gln (c.2153G>A) pathogenic?

BAP1 p.Arg718Gln (c.2153G>A) is classified Uncertain significance in BAP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-07-16). AlphaMissense: likely pathogenic (0.9167); Very rare (popmax 0.00177%, amr); Associated with BAP1-related tumor predisposition syndrome.

What condition is associated with BAP1 p.Arg718Gln (c.2153G>A)?

BAP1 p.Arg718Gln (c.2153G>A) is associated with BAP1-related tumor predisposition syndrome, hereditary neoplastic syndrome, neurodevelopmental disorder (ClinVar).

How common is BAP1 p.Arg718Gln (c.2153G>A) in the general population?

BAP1 p.Arg718Gln (c.2153G>A) is very rare (popmax 0.00177%, amr) (gnomAD).

How is BAP1-related tumor predisposition syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about BAP1 p.Arg718Gln (c.2153G>A)?

AlphaMissense predicts likely pathogenic (score 0.9167) — an in-silico prediction, not a clinical call.

BAP1 p.Arg718Gln

c.2153G>A · rs1440748203 · VCV1173084

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9167 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00177%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

BAP1-related tumor predisposition syndrome

Computational evidence

Protein change
AlphaMissense	0.9167	likely pathogenic
REVEL	0.294	indeterminate
SaProt	LLR -7.16	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.87, phastCons 1
Overall
CADD	27.3	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 0.00177% Admixed American · 1/56,488 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000208% 3/1,442,328 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00177%	56,488
European (non-Finnish)	0.000171%	586,067

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.Arg718Gln
Coding: c.2153G>A
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs1440748203
Type: single nucleotide variant
Location: chr3:52402325 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB

Full BAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Also linked: hereditary neoplastic syndrome neurodevelopmental disorder

For BAP1-related tumor predisposition syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

BAP1 p.Arg718= Likely benign ★★ same residue
BAP1 p.Arg718Trp Conflicting classifications of pathogenicity ★ ⚠ 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
BAP1 c.1251-1G>A 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-arg718gln (accessed [today's date]).

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