Is BAP1 p.Gln712Pro (c.2135A>C) pathogenic?

BAP1 p.Gln712Pro (c.2135A>C) is classified Uncertain significance in BAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-31). AlphaMissense: likely pathogenic (0.6095); Very rare (popmax 8.55e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Gln712Pro (c.2135A>C)?

BAP1 p.Gln712Pro (c.2135A>C) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Gln712Pro (c.2135A>C) in the general population?

BAP1 p.Gln712Pro (c.2135A>C) is very rare (popmax 8.55e-05%, nfe) (gnomAD).

What do computational predictors say about BAP1 p.Gln712Pro (c.2135A>C)?

AlphaMissense predicts likely pathogenic (score 0.6095) — an in-silico prediction, not a clinical call.

BAP1 p.Gln712Pro

c.2135A>C · rs2153226096 · VCV1391525

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6095 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.55e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.6095	likely pathogenic
REVEL	0.383	indeterminate
SaProt	LLR -5.32	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 7.9	GERP 1.9, phastCons 1
Overall
CADD	26.9	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 8.55e-05% European (non-Finnish) · 1/1,169,300 alleles

Overall 6.96e-05% 1/1,437,050 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.Gln712Pro
Coding: c.2135A>C
MANE Select: NM_004656
dbSNP: rs2153226096
Type: single nucleotide variant
Location: chr3:52402343 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 712: the 'disordered' region; a turn; 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.Gln712= Conflicting classifications of pathogenicity ★ same residue
BAP1 p.Gln712Glu 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-gln712pro (accessed [today's date]).

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