Is BAP1 p.Pro621= (c.1863C>G) pathogenic?

BAP1 p.Pro621= (c.1863C>G) is classified Benign/Likely benign in BAP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-23). Very rare (popmax 0.00439%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Pro621= (c.1863C>G)?

BAP1 p.Pro621= (c.1863C>G) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Pro621= (c.1863C>G) in the general population?

BAP1 p.Pro621= (c.1863C>G) is very rare (popmax 0.00439%, sas) (gnomAD).

BAP1 p.Pro621=

c.1863C>G · rs752636233 · VCV3224446

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP -2.2, phastCons 1
Overall
CADD	8.121	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,078 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000274% 4/1,461,662 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.Pro621=
Coding: c.1863C>G
MANE Select: NM_004656
dbSNP: rs752636233
Type: single nucleotide variant
Location: chr3:52403165 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 621: a UniProt-annotated variant site (in tpds1); the 'disordered' region; 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.Pro621Ser Uncertain significance ★★ ⚠ same residue
BAP1 p.Pro621Leu Uncertain significance ★ ⚠ same residue
BAP1 p.Pro621Thr 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

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-pro621 (accessed [today's date]).

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