KIF5A p.Phe136=
c.408T>C · rs770202664 · VCV1594655
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00161%, nfe)
Conditions
1
Spastic paraplegia
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 4.2 | GERP 1.3, phastCons 1 |
| Overall | ||
| CADD | 12.33 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00161%
European (non-Finnish) · 19/1,178,456 alleles
Filtering AF
0.00103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000831%
Overall
0.00124%
20/1,612,426 alleles · very rare
exomes 20/1,460,066 · genomes 0/152,360 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00161% | 62,024 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,436 |
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
- KIF5A
- Protein
- p.Phe136=
- Coding
- c.408T>C
- MANE Select
- NM_004984
- dbSNP
- rs770202664
- Type
- single nucleotide variant
- Location
- chr12:57564471 (GRCh38)
- Gene constraint
- LOEUF 0.315 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 76.04 · 4 PDB
- Residue 136
- the kinesin motor domain
Similar variants
- KIF5A c.3020+1G>A Pathogenic/Likely pathogenic ★★ same condition
- KIF5A c.3020+1G>C Pathogenic ★★ same condition
- KIF5A p.Arg1007Gly Pathogenic/Likely pathogenic ★★ same condition
- KIF5A p.Arg1007Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
- KIF5A p.Arg162Trp Pathogenic/Likely pathogenic ★★ same condition
- KIF5A p.Arg280His Pathogenic/Likely pathogenic ★★ same condition
- KIF5A p.Arg323Trp Pathogenic/Likely pathogenic ★★ same condition
- KIF5A p.Arg460Ter Pathogenic ★★ same condition
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/kif5a-p-phe136 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown