Is BAP1 p.Asp407= (c.1221T>C) pathogenic?

BAP1 p.Asp407= (c.1221T>C) is classified Benign/Likely benign in BAP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-31). Very rare (popmax 0.00223%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Asp407= (c.1221T>C)?

BAP1 p.Asp407= (c.1221T>C) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Asp407= (c.1221T>C) in the general population?

BAP1 p.Asp407= (c.1221T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

BAP1 p.Asp407=

c.1221T>C · rs1028053412 · VCV490780

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -3.5
Overall
CADD	0.065	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,898 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000867% 14/1,614,094 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,898
Admixed American	0.00167%	59,992
African / African-American	0.00133%	74,940
European (non-Finnish)	0.000932%	107,277

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.Asp407=
Coding: c.1221T>C
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs1028053412
Type: single nucleotide variant
Location: chr3:52404482 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB

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.Asp407Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 p.Asp407Glu 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-asp407 (accessed [today's date]).

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