Is BAP1 p.Ile706= (c.2118C>T) pathogenic?

BAP1 p.Ile706= (c.2118C>T) is classified Benign/Likely benign in BAP1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-21). Very rare (popmax 0.00458%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Ile706= (c.2118C>T)?

BAP1 p.Ile706= (c.2118C>T) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Ile706= (c.2118C>T) in the general population?

BAP1 p.Ile706= (c.2118C>T) is very rare (popmax 0.00458%, eas) (gnomAD).

BAP1 p.Ile706=

c.2118C>T · rs201122466 · VCV490844

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00458%, eas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.391	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.36	GERP -3.9
Overall
CADD	6.398	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00458% East Asian · 2/43,672 alleles

Filtering AF 0.000889% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000727%

Overall 0.00139% 22/1,581,668 alleles · very rare exomes 21/1,429,308 · genomes 1/152,360 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00458%	21,836
Admixed American	0.00184%	54,282
Remaining individualsnot grpmax-eligible	0.00163%	61,392
European (non-Finnish)	0.00146%	68,543
African / African-American	0.00134%	74,710

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.Ile706=
Coding: c.2118C>T
MANE Select: NM_004656
dbSNP: rs201122466
Type: single nucleotide variant
Location: chr3:52402360 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 706: the 'disordered' region; a UniProt-annotated variant site (in tpds1); 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

Also linked: BAP1-related tumor predisposition syndrome

Similar variants

BAP1 p.Ile706Val Uncertain significance ★★ ⚠ same residue
BAP1 p.Ile706Met 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.122+5G>A Pathogenic/Likely pathogenic ★★ same condition
BAP1 c.122+5G>C 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-ile706 (accessed [today's date]).

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