KL p.Pro648=
c.1944G>A · rs533689244 · VCV1929704
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0201%, eas)
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 -8.8 | GERP -3.5 |
| Overall | ||
| CADD | 0.137 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0201%
East Asian · 9/44,820 alleles
Filtering AF
0.0104%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0078%
Overall
0.00229%
37/1,612,334 alleles · ultra-rare
exomes 31/1,459,976 · genomes 6/152,358 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0201% | 4,980 |
| Admixed American | 0.00334% | 29,982 |
| African / African-American | 0.00267% | 37,517 |
| South Asian | 0.0022% | 45,493 |
| European (non-Finnish) | 0.00178% | 56,127 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,374 |
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.Pro648=
- Coding
- c.1944G>A
- MANE Select
- NM_004795
- dbSNP
- rs533689244
- Type
- single nucleotide variant
- Location
- chr13:33061023 (GRCh38)
- Gene constraint
- LOEUF 0.917 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.48 · 6 PDB
- Residue 648
- the 'glycosyl hydrolase-1 2' region
Similar variants
- 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
- KL p.Arg181Gln 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-pro648 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown