BPTF p.Ala1221=
c.3663C>G · rs9909489 · VCV2125067
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 36.1%, afr) — too common for a highly-penetrant pathogenic allele
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 0.4 | GERP -1.2 |
| Overall | ||
| CADD | 0.745 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
36.1%
African / African-American · 27,023/74,866 alleles
Filtering AF
35.7%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 35.6%
Overall
1.9%
30,689/1,613,828 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 36.1% | 3 |
| Remaining individualsnot grpmax-eligible | 2.49% | 40 |
| Admixed American | 2.36% | 42 |
| Middle Eastern | 1.57% | 64 |
| South Asian | 0.0966% | 1,035 |
| European (non-Finnish) | 0.0429% | 2,332 |
| East Asian | 0.00223% | 44,876 |
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
- BPTF
- Protein
- p.Ala1221=
- Coding
- c.3663C>G
- MANE Select
- NM_182641
- dbSNP
- rs9909489
- Type
- single nucleotide variant
- Location
- chr17:67911547 (GRCh38)
- Gene constraint
- LOEUF 0.09 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 1221
- the 'disordered' region
Similar variants
- BPTF p.Arg1322Ter Pathogenic/Likely pathogenic ★★ same type
- BPTF p.Arg1738Ter Pathogenic/Likely pathogenic ★★ same type
- BPTF p.Arg2858Ter Pathogenic ★★ same type
- BPTF p.Arg841Ter Pathogenic ★★ same type
- BPTF c.1864+562A>T Uncertain significance ★★ same type
- BPTF c.1865-5651C>G Uncertain significance ★★ ⚠ same type
- BPTF p.Ala1197Val Uncertain significance ★★ ⚠ same type
- BPTF p.Ala1252Val Uncertain significance ★★ ⚠ same type
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/bptf-p-ala1221 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown