Is BAP1 p.Glu212Lys (c.634G>A) pathogenic?

BAP1 p.Glu212Lys (c.634G>A) is classified Uncertain significance in BAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-28). AlphaMissense: likely pathogenic (0.9953); No allele count reported in gnomAD v4.1 (AN 1,562,486); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Glu212Lys (c.634G>A)?

BAP1 p.Glu212Lys (c.634G>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Glu212Lys (c.634G>A) in the general population?

BAP1 p.Glu212Lys (c.634G>A) is no allele count reported in gnomAD v4.1 (AN 1,562,486) (gnomAD).

What do computational predictors say about BAP1 p.Glu212Lys (c.634G>A)?

AlphaMissense predicts likely pathogenic (score 0.9953) — an in-silico prediction, not a clinical call.

BAP1 p.Glu212Lys

c.634G>A · VCV4867371

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9953 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,562,486)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9953	likely pathogenic
REVEL	0.4	indeterminate
SaProt	LLR -10.15	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Overall
CADD	27.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,562,486). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BAP1
Protein: p.Glu212Lys
Coding: c.634G>A
MANE Select: NM_004656
Type: single nucleotide variant
Location: chr3:52406854 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 212: the uch catalytic domain; an α-helix

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

Similar variants

BAP1 p.Glu212Met Uncertain significance ★ same residue
BAP1 p.Glu212Ter Pathogenic ★ same residue
BAP1 p.Glu212Gln 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.1251-1G>A Likely pathogenic ★★ same condition
BAP1 c.1251-2A>G 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-glu212lys (accessed [today's date]).

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