KL p.Phe464=
c.1392C>T · rs751485574 · VCV3015573
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.272%, 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 -7.2 | GERP -3.8 |
| Overall | ||
| CADD | 2.379 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.272%
East Asian · 122/44,900 alleles
Filtering AF
0.232%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.218%
Overall
0.00942%
152/1,614,012 alleles · rare
exomes 148/1,461,888 · genomes 4/152,124 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.272% | 368 |
| Finnishnot grpmax-eligible | 0.00781% | 12,804 |
| Admixed American | 0.005% | 20,002 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,606 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,243 |
| European (non-Finnish) | 0.00161% | 62,107 |
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.Phe464=
- Coding
- c.1392C>T
- MANE Select
- NM_004795
- dbSNP
- rs751485574
- Type
- single nucleotide variant
- Location
- chr13:33055108 (GRCh38)
- Gene constraint
- LOEUF 0.917 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.48 · 6 PDB
- Residue 464
- the 'glycosyl hydrolase-1 1' region
Similar variants
- KL p.Phe464fs 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-phe464 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown