Is BAP1 p.Tyr173= (c.519T>C) pathogenic?

BAP1 p.Tyr173= (c.519T>C) is classified Benign/Likely benign in BAP1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-28). Rare (popmax 0.199%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Tyr173= (c.519T>C)?

BAP1 p.Tyr173= (c.519T>C) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Tyr173= (c.519T>C) in the general population?

BAP1 p.Tyr173= (c.519T>C) is rare (popmax 0.199%, afr) (gnomAD).

BAP1 p.Tyr173=

c.519T>C · rs143901408 · VCV240061

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.199%, afr)

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 0.007	GERP -1.2, phastCons 0.018
Overall
CADD	5.771	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.199% African / African-American · 149/75,052 alleles

Filtering AF 0.172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.163%

Overall 0.0107% 172/1,614,174 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.199%	504
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0144%	6,946
Admixed American	0.0133%	7,503
South Asian	0.00329%	30,363
East Asian	0.00223%	44,876
European (non-Finnish)	8.47e-05%	1,180,026

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.Tyr173=
Coding: c.519T>C
MANE Select: NM_004656
dbSNP: rs143901408
Type: single nucleotide variant
Location: chr3:52407235 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 173: the uch catalytic domain; a β-strand

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.Tyr173Ter Pathogenic ★ same residue
BAP1 p.Tyr173Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 p.Tyr173fs 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
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-tyr173 (accessed [today's date]).

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