SPTB p.Asp27=
c.81C>T · rs778900824 · VCV2961896
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0111%, eas)
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 0.15 | GERP -5, phastCons 0.76 |
| Overall | ||
| CADD | 11.17 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0111%
East Asian · 5/44,886 alleles
Filtering AF
0.00434%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00276%
Overall
0.00105%
17/1,614,010 alleles · ultra-rare
exomes 14/1,461,818 · genomes 3/152,192 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0111% | 8,977 |
| African / African-American | 0.004% | 24,976 |
| Admixed American | 0.00333% | 30,003 |
| South Asian | 0.0011% | 91,074 |
| European (non-Finnish) | 0.000508% | 196,675 |
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.Asp27=
- Coding
- c.81C>T
- MANE Select
- NM_001355436
- dbSNP
- rs778900824
- Type
- single nucleotide variant
- Location
- chr14:64823014 (GRCh38)
- Gene constraint
- LOEUF 0.228 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 79.55 · 6 PDB
- Residue 27
- the 'disordered' region; the 'actin-binding' region
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-asp27 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown