SPTB p.Pro877=
c.2631A>T · rs374994056 · VCV2724448
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.09%, sas)
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 -3.8 |
| Overall | ||
| CADD | 5.379 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.09%
South Asian · 993/91,088 alleles
Filtering AF
1.03%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.01%
Overall
0.065%
1,049/1,614,006 alleles · low-frequency
exomes 993/1,461,684 · genomes 56/152,322 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 1.09% | 92 |
| Remaining individualsnot grpmax-eligible | 0.0736% | 1,359 |
| Middle Eastern | 0.0495% | 2,021 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,606 |
| East Asian | 0.00223% | 44,874 |
| European (non-Finnish) | 0.000424% | 236,008 |
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.Pro877=
- Coding
- c.2631A>T
- MANE Select
- NM_001355436
- dbSNP
- rs374994056
- Type
- single nucleotide variant
- Location
- chr14:64793032 (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-pro877 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown