SPTA1 p.Phe2045=
c.6135C>T · VCV4683597
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00802%, afr)
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 5.9 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 11.39 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00802%
African / African-American · 6/74,824 alleles
Filtering AF
0.00443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00403%
Overall
0.00465%
75/1,612,682 alleles · very rare
exomes 67/1,460,638 · genomes 8/152,044 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00802% | 12,471 |
| European (non-Finnish) | 0.00551% | 18,154 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,787 |
| Admixed American | 0.00167% | 59,990 |
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.Phe2045=
- Coding
- c.6135C>T
- MANE Select
- NM_003126
- Type
- single nucleotide variant
- Location
- chr1:158620452 (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-phe2045 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown