SPTB p.Phe450=
c.1350T>C · rs140380323 · VCV2063587
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.4 | GERP -5.7 |
| Overall | ||
| CADD | 0.489 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1%
African / African-American · 752/74,942 alleles
Filtering AF
0.944%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.92%
Overall
0.0522%
842/1,613,838 alleles · low-frequency
exomes 419/1,461,756 · genomes 423/152,082 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1% | 100 |
| Remaining individualsnot grpmax-eligible | 0.0672% | 1,488 |
| Admixed American | 0.0533% | 1,875 |
| Middle Eastern | 0.0165% | 6,052 |
| South Asian | 0.0022% | 45,532 |
| European (non-Finnish) | 0.0011% | 90,767 |
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
- SPTB
- Protein
- p.Phe450=
- Coding
- c.1350T>C
- MANE Select
- NM_001355436
- dbSNP
- rs140380323
- Type
- single nucleotide variant
- Location
- chr14:64795631 (GRCh38)
- Gene constraint
- LOEUF 0.228 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 79.55 · 6 PDB
Similar variants
- SPTB c.1064+1G>A Pathogenic ★★ same type
- SPTB c.1341+1G>A Likely pathogenic ★★ same type
- SPTB c.3764+1G>A Pathogenic/Likely pathogenic ★★ same type
- SPTB c.474+1G>A Likely pathogenic ★★ same type
- SPTB c.474+1G>T Pathogenic/Likely pathogenic ★★ same type
- SPTB c.4843-1G>T Likely pathogenic ★★ same type
- SPTB c.4973+5G>A Pathogenic/Likely pathogenic ★★ same type
- SPTB c.5178+1G>A Likely pathogenic ★★ 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/sptb-p-phe450 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown