SPTA1 p.Lys321=
c.963G>A · VCV4763636
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00134%, afr)
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 0.006 | GERP 0.1, phastCons 0.8 |
| Overall | ||
| CADD | 8.181 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00134%
African / African-American · 1/74,868 alleles
Filtering AF
0.000359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00026%
Overall
0.00062%
10/1,613,396 alleles · very rare
exomes 6/1,461,256 · genomes 4/152,140 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00134% | 74,868 |
| European (non-Finnish) | 0.000763% | 131,072 |
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.Lys321=
- Coding
- c.963G>A
- MANE Select
- NM_003126
- Type
- single nucleotide variant
- Location
- chr1:158676290 (GRCh38)
- Gene constraint
- LOEUF 0.591 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.74 · 3 PDB
Similar variants
- 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
- SPTA1 c.4339-99C>T 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/spta1-p-lys321 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown