KL p.Ser46=
c.138G>C · rs2501695156 · VCV2797563
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0196%, mid)
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 0.26 | GERP -0.92, phastCons 0.92 |
| Overall | ||
| CADD | 4.368 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0196%
Middle Eastern · 1/5,096 alleles
Overall
0.000135%
2/1,482,472 alleles · ultra-rare
exomes 2/1,330,828 · genomes 0/151,644 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0196% | 5,096 |
| European (non-Finnish) | 8.94e-05% | 1,118,578 |
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
- KL
- Protein
- p.Ser46=
- Coding
- c.138G>C
- MANE Select
- NM_004795
- dbSNP
- rs2501695156
- Type
- single nucleotide variant
- Location
- chr13:33016578 (GRCh38)
- Gene constraint
- LOEUF 0.917 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.48 · 6 PDB
- Residue 46
- a β-strand
Similar variants
- KL p.Ser46Leu Uncertain significance ★ ⚠ same residue
- KL c.1331-3C>A Uncertain significance ★★ same type
- KL p.Ala3Thr Uncertain significance ★★ ⚠ same type
- KL p.Ala50Val Uncertain significance ★★ ⚠ same type
- KL p.Ala656Thr Uncertain significance ★★ ⚠ same type
- KL p.Ala663Thr Uncertain significance ★★ ⚠ same type
- KL p.Ala987Thr Uncertain significance ★★ ⚠ same type
- KL p.Arg179Trp 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/kl-p-ser46 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown