Is BAP1 p.Lys120Glu (c.358A>G) pathogenic?

BAP1 p.Lys120Glu (c.358A>G) is classified Conflicting classifications of pathogenicity in BAP1 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-10-13). AlphaMissense: ambiguous (0.3624); Very rare (popmax 0.00339%, nfe); Associated with BAP1-related tumor predisposition syndrome.

What condition is associated with BAP1 p.Lys120Glu (c.358A>G)?

BAP1 p.Lys120Glu (c.358A>G) is associated with BAP1-related tumor predisposition syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Lys120Glu (c.358A>G) in the general population?

BAP1 p.Lys120Glu (c.358A>G) is very rare (popmax 0.00339%, nfe) (gnomAD).

How is BAP1-related tumor predisposition syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about BAP1 p.Lys120Glu (c.358A>G)?

AlphaMissense predicts ambiguous (score 0.3624) — an in-silico prediction, not a clinical call.

BAP1 p.Lys120Glu

c.358A>G · rs774573926 · VCV489634

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

ambiguous

0.3624 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00339%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

BAP1-related tumor predisposition syndrome

Computational evidence

Protein change
AlphaMissense	0.3624	ambiguous
REVEL	0.164	moderately benign-leaning
SaProt	LLR -8.92	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.8, phastCons 1
Overall
CADD	24.8	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 0.00339% European (non-Finnish) · 40/1,179,994 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00225%

Overall 0.00294% 43/1,461,614 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00339%	29,500
Admixed American	0.00167%	60,016
Remaining individualsnot grpmax-eligible	0.0016%	62,498
African / African-American	0.00133%	75,044

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.Lys120Glu
Coding: c.358A>G
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs774573926
Type: single nucleotide variant
Location: chr3:52407975 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB
Residue 120: the 'interaction with hip2' region

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

Disease context

Also linked: hereditary neoplastic syndrome

For BAP1-related tumor predisposition syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

BAP1 p.Lys120Thr Uncertain significance ★★ ⚠ same residue
BAP1 p.Lys120= Benign/Likely benign ★★ same residue
BAP1 p.Lys120Arg Uncertain significance ★ ⚠ same residue
BAP1 p.Lys120fs Pathogenic ★ same residue
BAP1 p.Lys120Ter Likely 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-lys120glu (accessed [today's date]).

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