KL p.Ala667=
c.2001A>G · VCV4747868
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0253%, sas)
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 -15 | GERP -3.8 |
| Overall | ||
| CADD | 0.002 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0253%
South Asian · 23/91,000 alleles
Filtering AF
0.0172%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0146%
Overall
0.0018%
29/1,613,162 alleles · ultra-rare
exomes 27/1,460,950 · genomes 2/152,212 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0253% | 3,957 |
| Remaining individualsnot grpmax-eligible | 0.00801% | 12,486 |
| European (non-Finnish) | 8.48e-05% | 1,179,440 |
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.Ala667=
- Coding
- c.2001A>G
- MANE Select
- NM_004795
- Type
- single nucleotide variant
- Location
- chr13:33061080 (GRCh38)
- Gene constraint
- LOEUF 0.917 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.48 · 6 PDB
- Residue 667
- an α-helix; 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-ala667 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown