Is BAP1 p.Arg213Pro (c.638G>C) pathogenic?

BAP1 p.Arg213Pro (c.638G>C) is classified Conflicting classifications of pathogenicity in BAP1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-03-27). AlphaMissense: likely pathogenic (0.9998); No allele count reported in gnomAD v4.1 (AN 1,560,782); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Arg213Pro (c.638G>C)?

BAP1 p.Arg213Pro (c.638G>C) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Arg213Pro (c.638G>C) in the general population?

BAP1 p.Arg213Pro (c.638G>C) is no allele count reported in gnomAD v4.1 (AN 1,560,782) (gnomAD).

What do computational predictors say about BAP1 p.Arg213Pro (c.638G>C)?

AlphaMissense predicts likely pathogenic (score 0.9998) — an in-silico prediction, not a clinical call.

BAP1 p.Arg213Pro

c.638G>C · rs1220529268 · VCV655445

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9998 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,560,782)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9998	likely pathogenic · top 5% in BAP1
REVEL	0.835	moderately pathogenic-leaning
SaProt	LLR -15.81	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Overall
CADD	32.0	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 1,560,782). 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.Arg213Pro
Coding: c.638G>C
MANE Select: NM_004656
dbSNP: rs1220529268
Type: single nucleotide variant
Location: chr3:52406850 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 213: the uch catalytic domain; an α-helix

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.Arg213Cys Uncertain significance ★★ ⚠ same residue
BAP1 p.Arg213His Uncertain significance ★★ ⚠ same residue
BAP1 p.Arg213= Likely benign ★★ same residue
BAP1 p.Arg213_Gly215dup 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-arg213pro (accessed [today's date]).

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