Is BAP1 p.Ile706Met (c.2118C>G) pathogenic?

BAP1 p.Ile706Met (c.2118C>G) is classified Uncertain significance in BAP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-09-01). AlphaMissense: likely pathogenic (0.8467); Absent from gnomAD v4.1; Associated with BAP1-related disorder.

What condition is associated with BAP1 p.Ile706Met (c.2118C>G)?

BAP1 p.Ile706Met (c.2118C>G) is associated with BAP1-related disorder (ClinVar).

How common is BAP1 p.Ile706Met (c.2118C>G) in the general population?

BAP1 p.Ile706Met (c.2118C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BAP1 p.Ile706Met (c.2118C>G)?

AlphaMissense predicts likely pathogenic (score 0.8467) — an in-silico prediction, not a clinical call.

BAP1 p.Ile706Met

c.2118C>G · VCV3347409

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8467 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

BAP1-related disorder

Computational evidence

Protein change
AlphaMissense	0.8467	likely pathogenic
REVEL	0.301	indeterminate
SaProt	LLR -6.55	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.36	GERP -3.9
Overall
CADD	17.04	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BAP1
Protein: p.Ile706Met
Coding: c.2118C>G
MANE Select: NM_007212 · reported on NM_004656
Type: single nucleotide variant
Location: chr3:52402360 (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.Ile706Val Uncertain significance ★★ ⚠ same residue
BAP1 p.Ile706= Benign/Likely benign ★★ 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
BAP1 p.Asp407Asn 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-ile706met (accessed [today's date]).

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