KIZ p.Pro461=
c.1383G>A · rs533329332 · VCV1166730
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0799%, nfe)
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 1.1 | GERP -1.7 |
| Overall | ||
| CADD | 4.467 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0799%
European (non-Finnish) · 910/1,139,212 alleles
Filtering AF
0.0755%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0738%
Overall
0.0606%
944/1,558,316 alleles · ultra-rare
exomes 890/1,406,098 · genomes 54/152,218 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0799% | 1,252 |
| Remaining individualsnot grpmax-eligible | 0.0346% | 2,887 |
| Admixed American | 0.00707% | 14,137 |
| African / African-American | 0.00543% | 18,409 |
| South Asian | 0.00348% | 28,722 |
| Finnishnot grpmax-eligible | 0.0032% | 31,298 |
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
- KIZ
- Protein
- p.Pro461=
- Coding
- c.1383G>A
- MANE Select
- NM_018474
- dbSNP
- rs533329332
- Type
- single nucleotide variant
- Location
- chr20:21205521 (GRCh38)
- Gene constraint
- LOEUF 1.227 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 54.82
- Residue 461
- the 'disordered' region
Similar variants
- KIZ p.Pro461Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- KIZ c.1447-2A>G Likely pathogenic ★★ same type
- KIZ c.1612+2T>G Likely pathogenic ★★ same type
- KIZ p.Arg195Ter Pathogenic/Likely pathogenic ★★ same type
- KIZ p.Arg76Ter Pathogenic ★★ same type
- KIZ p.Gln199Ter Pathogenic/Likely pathogenic ★★ same type
- KIZ p.Gln22Ter Pathogenic/Likely pathogenic ★★ same type
- KIZ p.Glu18Ter 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/kiz-p-pro461 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown