LPL p.Ile443=
c.1329C>A · VCV4070171
Uncertain significance
No assertion criteria
Classification
Uncertain significance
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
Conditions
1
familial lipoprotein lipase deficiency
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 1.1 | GERP -0.41, phastCons 1 |
| Overall | ||
| CADD | 6.837 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,874 alleles
Filtering AF
0.000443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000372%
6/1,611,114 alleles · very rare
exomes 5/1,458,920 · genomes 1/152,194 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,437 |
| Admixed American | 0.00167% | 59,988 |
| European (non-Finnish) | 0.000255% | 392,468 |
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
- LPL
- Protein
- p.Ile443=
- Coding
- c.1329C>A
- MANE Select
- NM_000237
- Type
- single nucleotide variant
- Location
- chr8:19962121 (GRCh38)
- Gene constraint
- LOEUF 1.075 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.36 · 5 PDB
- Residue 443
- a β-strand; the plat domain; the 'interaction with gpihbp1' region
Similar variants
- LPL c.1019-2A>T Pathogenic ★★ same condition
- LPL c.1019-3C>A Pathogenic/Likely pathogenic ★★ same condition
- LPL c.1139+1G>A Likely pathogenic ★★ same condition
- LPL c.1139+7A>G Likely pathogenic ★★ same condition
- LPL c.249+1G>A Pathogenic ★★ same condition
- LPL c.89-1G>A Pathogenic/Likely pathogenic ★★ same condition
- LPL c.89-1G>C Pathogenic/Likely pathogenic ★★ same condition
- LPL p.Ala98Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
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/lpl-p-ile443 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown