KIZ p.Asp545=
c.1635C>T · rs762088996 · VCV1143517
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.23 | acceptor loss · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -8.1 | GERP -5 |
| Overall | ||
| CADD | 0.062 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,070 alleles
Filtering AF
0.000445%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000212%
Overall
0.00081%
13/1,604,528 alleles · ultra-rare
exomes 11/1,452,722 · genomes 2/151,806 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,070 |
| African / African-American | 0.00268% | 37,284 |
| South Asian | 0.00223% | 44,893 |
| European (non-Finnish) | 0.000682% | 146,711 |
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.Asp545=
- Coding
- c.1635C>T
- MANE Select
- NM_018474
- dbSNP
- rs762088996
- Type
- single nucleotide variant
- Location
- chr20:21215605 (GRCh38)
- Gene constraint
- LOEUF 1.227 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 54.82
Similar variants
- 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
- KIZ p.Leu625Ter 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-asp545 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown