SPTA1 p.Val286=
c.858A>G · rs370463832 · VCV1330946
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
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 | GERP -3.7 |
| Overall | ||
| CADD | 0.843 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,056 alleles
Filtering AF
0.0154%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0124%
Overall
0.00843%
136/1,613,628 alleles · ultra-rare
exomes 127/1,461,470 · genomes 9/152,158 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,028 |
| Admixed American | 0.025% | 3,997 |
| African / African-American | 0.0173% | 5,767 |
| Finnishnot grpmax-eligible | 0.0125% | 8,002 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,926 |
| European (non-Finnish) | 0.00771% | 12,964 |
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
- SPTA1
- Protein
- p.Val286=
- Coding
- c.858A>G
- MANE Select
- NM_003126
- dbSNP
- rs370463832
- Type
- single nucleotide variant
- Location
- chr1:158677789 (GRCh38)
- Gene constraint
- LOEUF 0.591 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.74 · 3 PDB
Similar variants
- SPTA1 p.Val286Leu Likely benign ★ same residue
- SPTA1 c.1350+1G>C Pathogenic/Likely pathogenic ★★ same type
- SPTA1 c.1833+1G>A Pathogenic/Likely pathogenic ★★ same type
- SPTA1 c.24+1G>A Pathogenic/Likely pathogenic ★★ same type
- SPTA1 c.2464+1G>A Likely pathogenic ★★ same type
- SPTA1 c.2806-13T>G Pathogenic/Likely pathogenic ★★ same type
- SPTA1 c.2898+2T>C Likely pathogenic ★★ same type
- SPTA1 c.390+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/spta1-p-val286 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown