SPTB p.Pro353=
c.1059G>A · rs369464948 · VCV3058741
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0126%, nfe)
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 -14 | GERP -5.5 |
| Overall | ||
| CADD | 0.389 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0126%
European (non-Finnish) · 149/1,180,024 alleles
Filtering AF
0.011%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0103%
Overall
0.0103%
167/1,614,004 alleles · ultra-rare
exomes 155/1,461,808 · genomes 12/152,196 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0126% | 7,920 |
| African / African-American | 0.00801% | 12,489 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,620 |
| South Asian | 0.00549% | 18,214 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,606 |
| East Asian | 0.00223% | 44,892 |
| Admixed American | 0.00167% | 60,012 |
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.Pro353=
- Coding
- c.1059G>A
- MANE Select
- NM_001355436
- dbSNP
- rs369464948
- Type
- single nucleotide variant
- Location
- chr14:64799752 (GRCh38)
- Gene constraint
- LOEUF 0.228 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 79.55 · 6 PDB
Similar variants
- SPTB p.Pro353Leu Uncertain significance ★★ ⚠ same residue
- 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
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-pro353 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown