Is BAP1 p.Val106Met (c.316G>A) pathogenic?

BAP1 p.Val106Met (c.316G>A) is classified Conflicting classifications of pathogenicity in BAP1 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-04-16). AlphaMissense: likely pathogenic (0.6086); Very rare (popmax 0.004%, afr); Associated with BAP1-related tumor predisposition syndrome.

What condition is associated with BAP1 p.Val106Met (c.316G>A)?

BAP1 p.Val106Met (c.316G>A) is associated with BAP1-related tumor predisposition syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Val106Met (c.316G>A) in the general population?

BAP1 p.Val106Met (c.316G>A) is very rare (popmax 0.004%, afr) (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.Val106Met (c.316G>A)?

AlphaMissense predicts likely pathogenic (score 0.6086) — an in-silico prediction, not a clinical call.

BAP1 p.Val106Met

c.316G>A · rs754385495 · VCV630500

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.6086 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

BAP1-related tumor predisposition syndrome

Computational evidence

Protein change
AlphaMissense	0.6086	likely pathogenic
REVEL	0.334	indeterminate
SaProt	LLR -8.75	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Overall
CADD	28.1	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 0.004% African / African-American · 3/74,912 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00062% 10/1,613,694 alleles · very rare exomes 7/1,461,530 · genomes 3/152,164 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,971
South Asian	0.0022%	45,495
Admixed American	0.00167%	59,970
European (non-Finnish)	0.000339%	294,979

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.Val106Met
Coding: c.316G>A
MANE Select: NM_004656
dbSNP: rs754385495
Type: single nucleotide variant
Location: chr3:52408017 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 106: the uch catalytic domain; a β-strand

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.Val106Leu 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
BAP1 c.1251-1G>C 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-val106met (accessed [today's date]).

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