SPAST p.Phe58=
c.174T>C · rs145571171 · VCV741499
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00935%, 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 -0.49 | GERP -3.6 |
| Overall | ||
| CADD | 10.42 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00935%
African / African-American · 7/74,880 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00309%
Overall
0.00093%
15/1,613,344 alleles · very rare
exomes 11/1,461,222 · genomes 4/152,122 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00935% | 10,697 |
| East Asian | 0.00223% | 44,840 |
| South Asian | 0.0011% | 91,074 |
| European (non-Finnish) | 0.000509% | 196,597 |
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
- SPAST
- Protein
- p.Phe58=
- Coding
- c.174T>C
- MANE Select
- NM_014946
- dbSNP
- rs145571171
- Type
- single nucleotide variant
- Location
- chr2:32064005 (GRCh38)
- Gene constraint
- LOEUF 0.69 · pLI 0.11 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.03 · 7 PDB
- Residue 58
- the 'required for interaction with ssna1 and microtubules' region; a UniProt-annotated variant site (in spg4); the 'required for interaction with rtn1' region; the 'required for midbody localization' region; the 'required for interaction with atl1' region
Similar variants
- SPAST c.1004+1G>C Pathogenic/Likely pathogenic ★★ same type
- SPAST c.1004+1G>T Pathogenic ★★ same type
- SPAST c.1004+2T>G Pathogenic ★★ same type
- SPAST c.1098+1G>A Pathogenic ★★ same type
- SPAST c.1099-1G>A Pathogenic ★★ same type
- SPAST c.1099-2A>C Pathogenic/Likely pathogenic ★★ same type
- SPAST c.1173+1G>A Pathogenic/Likely pathogenic ★★ same type
- SPAST c.1174-1G>A 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/spast-p-phe58 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown