Is BAP1 p.Arg722Cys (c.2164C>T) pathogenic?

BAP1 p.Arg722Cys (c.2164C>T) is classified Uncertain significance in BAP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-10-31). AlphaMissense: likely pathogenic (0.9428); No allele count reported in gnomAD v4.1 (AN 1,598,062); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Arg722Cys (c.2164C>T)?

BAP1 p.Arg722Cys (c.2164C>T) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Arg722Cys (c.2164C>T) in the general population?

BAP1 p.Arg722Cys (c.2164C>T) is no allele count reported in gnomAD v4.1 (AN 1,598,062) (gnomAD).

What do computational predictors say about BAP1 p.Arg722Cys (c.2164C>T)?

AlphaMissense predicts likely pathogenic (score 0.9428) — an in-silico prediction, not a clinical call.

BAP1 p.Arg722Cys

c.2164C>T · rs771007826 · VCV569962

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9428 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,598,062)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9428	likely pathogenic
REVEL	0.229	benign-leaning
SaProt	LLR -8.46	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 9.9	GERP 0.86, phastCons 1
Overall
CADD	33.0	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

No allele count reported in gnomAD v4.1 (AN 1,598,062). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BAP1
Protein: p.Arg722Cys
Coding: c.2164C>T
MANE Select: NM_004656
dbSNP: rs771007826
Type: single nucleotide variant
Location: chr3:52402314 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 722: the 'disordered' region; the 'positively charged c-terminal extension (cte)' region; a UniProt-annotated variant site (in tpds1)

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.Arg722Gly Uncertain significance ★ ⚠ same residue
BAP1 p.Arg722His Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 p.Arg722= Likely benign ★ 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-arg722cys (accessed [today's date]).

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