Is BAP1 p.Arg545His (c.1634G>A) pathogenic?

BAP1 p.Arg545His (c.1634G>A) is classified Conflicting classifications of pathogenicity in BAP1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-31). AlphaMissense: ambiguous (0.5583); Very rare (popmax 0.00223%, eas); Associated with BAP1-related disorder.

What condition is associated with BAP1 p.Arg545His (c.1634G>A)?

BAP1 p.Arg545His (c.1634G>A) is associated with BAP1-related disorder, BAP1-related tumor predisposition syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Arg545His (c.1634G>A) in the general population?

BAP1 p.Arg545His (c.1634G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about BAP1 p.Arg545His (c.1634G>A)?

AlphaMissense predicts ambiguous (score 0.5583) — an in-silico prediction, not a clinical call.

BAP1 p.Arg545His

c.1634G>A · rs71651687 · VCV485277

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.5583 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

BAP1-related disorder

Computational evidence

Protein change
AlphaMissense	0.5583	ambiguous
REVEL	0.333	indeterminate
SaProt	LLR -6.75	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Overall
CADD	26.0	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

Grpmax group 0.00223% East Asian · 1/44,896 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000434% 7/1,613,946 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,896
European (non-Finnish)	0.000508%	196,667

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.Arg545His
Coding: c.1634G>A
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs71651687
Type: single nucleotide variant
Location: chr3:52403511 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB

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

Disease context

BAP1-related disorder

Also linked: BAP1-related tumor predisposition syndrome hereditary neoplastic syndrome

Similar variants

BAP1 p.Arg545Cys Uncertain significance ★★ ⚠ same residue
BAP1 p.Arg545Gly Uncertain significance ★ ⚠ same residue
BAP1 p.Arg545Pro 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
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-arg545his (accessed [today's date]).

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