Is BAP1 p.Lys601Glu (c.1801A>G) pathogenic?

BAP1 p.Lys601Glu (c.1801A>G) is classified Conflicting classifications of pathogenicity in BAP1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-11-24). AlphaMissense: likely benign (0.0696); Ultra-rare (popmax 0.022%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Lys601Glu (c.1801A>G)?

BAP1 p.Lys601Glu (c.1801A>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Lys601Glu (c.1801A>G) in the general population?

BAP1 p.Lys601Glu (c.1801A>G) is ultra-rare (popmax 0.022%, sas) (gnomAD).

What do computational predictors say about BAP1 p.Lys601Glu (c.1801A>G)?

AlphaMissense predicts likely benign (score 0.0696) — an in-silico prediction, not a clinical call.

BAP1 p.Lys601Glu

c.1801A>G · rs142059527 · VCV485252

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0696 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0696	likely benign
REVEL	0.265	benign-leaning
SaProt	LLR -5.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 0.99, phastCons 1
Overall
CADD	19.73	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 0.022% South Asian · 20/91,084 alleles

Filtering AF 0.0145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00186% 30/1,614,134 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.022%	4,554
Middle Eastern	0.0165%	6,062
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
Remaining individualsnot grpmax-eligible	0.0032%	31,254
European (non-Finnish)	0.000508%	196,671

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.Lys601Glu
Coding: c.1801A>G
MANE Select: NM_004656
dbSNP: rs142059527
Type: single nucleotide variant
Location: chr3:52403227 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 601: 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

Similar variants

BAP1 p.Lys601= Likely benign ★★ same residue
BAP1 p.Lys601Ter Pathogenic ★ same residue
BAP1 p.Lys601del Conflicting classifications of pathogenicity ★ same residue
BAP1 p.Lys601Asn 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.1251-1G>A 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-lys601glu (accessed [today's date]).

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