Is BAP1 p.Lys240Thr (c.719A>C) pathogenic?

BAP1 p.Lys240Thr (c.719A>C) is classified Uncertain significance in BAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-11). AlphaMissense: ambiguous (0.4627); Very rare (popmax 0.00133%, afr); Associated with BAP1-related disorder.

What condition is associated with BAP1 p.Lys240Thr (c.719A>C)?

BAP1 p.Lys240Thr (c.719A>C) is associated with BAP1-related disorder (ClinVar).

How common is BAP1 p.Lys240Thr (c.719A>C) in the general population?

BAP1 p.Lys240Thr (c.719A>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about BAP1 p.Lys240Thr (c.719A>C)?

AlphaMissense predicts ambiguous (score 0.4627) — an in-silico prediction, not a clinical call.

BAP1 p.Lys240Thr

c.719A>C · rs2153227461 · VCV2633992

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4627 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

BAP1-related disorder

Computational evidence

Protein change
AlphaMissense	0.4627	ambiguous
REVEL	0.113	moderately benign-leaning
SaProt	LLR -8.92	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.47 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Overall
CADD	26.6	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 0.00133% African / African-American · 1/75,058 alleles

Overall 6.84e-05% 1/1,461,846 alleles · very rare

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.Lys240Thr
Coding: c.719A>C
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs2153227461
Type: single nucleotide variant
Location: chr3:52406317 (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

Similar variants

BAP1 p.Lys240= Benign/Likely benign ★★ same residue
BAP1 p.Lys240Ter Pathogenic ★ same residue
BAP1 p.Lys240Asn Uncertain significance ★ ⚠ same residue
BAP1 p.Met1Arg Pathogenic/Likely pathogenic ★★ same condition
BAP1 p.Ile263Val Uncertain significance ★★ ⚠ same condition
BAP1 p.Ser455Pro Uncertain significance ★★ ⚠ same condition
BAP1 p.Tyr33His Likely pathogenic ★ same condition
BAP1 p.Arg545His Conflicting classifications of pathogenicity ★ ⚠ 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-lys240thr (accessed [today's date]).

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