Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 11.2%, afr) — too common for a highly-penetrant pathogenic allele
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 -0.93 | GERP -2.8 |
| Overall | ||
| CADD | 1.311 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
11.2%
African / African-American · 8,431/74,974 alleles
Filtering AF
11%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 11%
Overall
0.604%
9,753/1,614,014 alleles · common
exomes 5,022/1,461,840 · genomes 4,731/152,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 11.2% | 9 |
| Remaining individualsnot grpmax-eligible | 0.75% | 133 |
| Admixed American | 0.725% | 138 |
| Middle Eastern | 0.594% | 168 |
| European (non-Finnish) | 0.0307% | 3,260 |
| South Asian | 0.022% | 4,554 |
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
- KLK4
- Protein
- p.Ser100=
- Coding
- c.300C>T
- MANE Select
- NM_004917
- dbSNP
- rs198966
- Type
- single nucleotide variant
- Location
- chr19:50908754 (GRCh38)
- Gene constraint
- LOEUF 1.467 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.60 · 18 PDB
- Residue 100
- the peptidase s1 domain
Similar variants
- KLK4 p.Trp153Ter Pathogenic/Likely pathogenic ★★ same type
- KLK4 p.Pro227Leu Uncertain significance ★★ ⚠ same type
- KLK4 c.224+182G>C Benign ★★ same type
- KLK4 c.224+193T>C Benign ★★ same type
- KLK4 c.224+92C>G Benign ★★ same type
- KLK4 c.61+132C>G Benign ★★ same type
- KLK4 c.61+144C>T Benign ★★ same type
- KLK4 c.61+28T>A Benign ★★ 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/klk4-p-ser100 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown