KIF2A p.Arg421=
c.1263A>G · rs758829591 · VCV1981203
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0634%, amr)
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 4.1 | GERP -0.95, phastCons 1 |
| Overall | ||
| CADD | 14.01 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0634%
Admixed American · 38/59,984 alleles
Filtering AF
0.0474%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0418%
Overall
0.00242%
39/1,612,512 alleles · ultra-rare
exomes 36/1,460,294 · genomes 3/152,218 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0634% | 1,579 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,424 |
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
- KIF2A
- Protein
- p.Arg421=
- Coding
- c.1263A>G
- MANE Select
- NM_001098511
- dbSNP
- rs758829591
- Type
- single nucleotide variant
- Location
- chr5:62363695 (GRCh38)
- Gene constraint
- LOEUF 0.617 · pLI 0.76 (gnomAD)
- Structure
- AlphaFold pLDDT 79.37 · 6 PDB
- Residue 421
- the kinesin motor domain; an α-helix
Similar variants
- KIF2A p.Glu73Lys Likely pathogenic ★★ ⚠ same type
- KIF2A p.Gly313Glu Likely pathogenic ★★ same type
- KIF2A p.Ser317Asn Pathogenic ★★ same type
- KIF2A p.Thr320Ile Pathogenic/Likely pathogenic ★★ same type
- KIF2A p.Ala144Thr Uncertain significance ★★ ⚠ same type
- KIF2A p.Arg117His Uncertain significance ★★ ⚠ same type
- KIF2A p.Arg154His Uncertain significance ★★ ⚠ same type
- KIF2A p.Arg402Trp Uncertain significance ★★ ⚠ 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/kif2a-p-arg421 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown