LPL p.Ala98=
c.294C>T · rs2540103158 · VCV2776411
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, nfe)
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 0.37 | GERP -2.3, phastCons 0.97 |
| Overall | ||
| CADD | 9.045 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,180,034 alleles
Overall
6.84e-05%
1/1,461,892 alleles · very rare
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.Ala98=
- Coding
- c.294C>T
- MANE Select
- NM_000237
- dbSNP
- rs2540103158
- Type
- single nucleotide variant
- Location
- chr8:19951813 (GRCh38)
- Gene constraint
- LOEUF 1.075 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.36 · 5 PDB
- Residue 98
- an α-helix; a UniProt-annotated variant site (in hlpp1; decreases the specific activity of the enzyme; reduces the secretion of the mutant protein significantly; the total lpl mass is reduced compared to that of the wild-type construct)
Similar variants
- LPL p.Ala98Thr Pathogenic/Likely pathogenic ★★ ⚠ same residue
- LPL p.Ala98Ser Uncertain significance ★ ⚠ same residue
- LPL c.1019-2A>T Pathogenic ★★ same type
- LPL c.1019-3C>A Pathogenic/Likely pathogenic ★★ same type
- LPL c.1139+1G>A Likely pathogenic ★★ same type
- LPL c.1139+7A>G Likely pathogenic ★★ same type
- LPL c.1322+1G>C Pathogenic/Likely pathogenic ★★ same type
- LPL c.249+1G>A Pathogenic ★★ 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/lpl-p-ala98 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown