SPTB p.Pro2085=
c.6255C>T · VCV3961576
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.02%, amr)
Conditions
1
Inborn genetic diseases
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 -4.1 | GERP -4.6 |
| Overall | ||
| CADD | 2.862 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.02%
Admixed American · 12/59,998 alleles
Filtering AF
0.0115%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00898%
Overall
0.00192%
31/1,613,894 alleles · ultra-rare
exomes 29/1,461,712 · genomes 2/152,182 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.02% | 5,000 |
| Middle Eastern | 0.0164% | 6,084 |
| East Asian | 0.00223% | 44,900 |
| Finnishnot grpmax-eligible | 0.00157% | 63,884 |
| European (non-Finnish) | 0.00136% | 73,752 |
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.Pro2085=
- Coding
- c.6255C>T
- MANE Select
- NM_001355436
- Type
- single nucleotide variant
- Location
- chr14:64767317 (GRCh38)
- Gene constraint
- LOEUF 0.228 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 79.55 · 6 PDB
- Residue 2085
- the 'disordered' region
Similar variants
- SPTB p.Ala1152Gly Uncertain significance ★★ ⚠ same condition
- SPTB p.Ala1180Thr Uncertain significance ★★ ⚠ same condition
- SPTB p.Ala1632Val Uncertain significance ★★ ⚠ same condition
- SPTB p.Ala1741Val Uncertain significance ★★ ⚠ same condition
- SPTB p.Ala1760Val Uncertain significance ★★ ⚠ same condition
- SPTB p.Ala1795Thr Uncertain significance ★★ ⚠ same condition
- SPTB p.Ala1903Val Uncertain significance ★★ ⚠ same condition
- SPTB p.Ala837Val Uncertain significance ★★ ⚠ 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/sptb-p-pro2085 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown