Is BAP1 p.Arg551Gly (c.1651C>G) pathogenic?

BAP1 p.Arg551Gly (c.1651C>G) is classified Uncertain significance in BAP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-06-14). AlphaMissense: likely pathogenic (0.8621); Very rare (popmax 0.00333%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Arg551Gly (c.1651C>G)?

BAP1 p.Arg551Gly (c.1651C>G) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Arg551Gly (c.1651C>G) in the general population?

BAP1 p.Arg551Gly (c.1651C>G) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about BAP1 p.Arg551Gly (c.1651C>G)?

AlphaMissense predicts likely pathogenic (score 0.8621) — an in-silico prediction, not a clinical call.

BAP1 p.Arg551Gly

c.1651C>G · rs755664216 · VCV472675

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.8621 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.8621	likely pathogenic
REVEL	0.173	moderately benign-leaning
SaProt	LLR -10.08	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Overall
CADD	24.2	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 0.00333% Admixed American · 2/60,028 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000274% 4/1,461,702 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,014
European (non-Finnish)	0.000169%	589,991

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.Arg551Gly
Coding: c.1651C>G
MANE Select: NM_004656
dbSNP: rs755664216
Type: single nucleotide variant
Location: chr3:52403494 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 551: 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.Arg551Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 p.Arg551His Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 p.Arg551Pro Uncertain significance ★ ⚠ same residue
BAP1 p.Arg551= Likely benign ★ same residue
BAP1 p.Arg551fs Pathogenic ★ 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

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-arg551gly (accessed [today's date]).

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