LPL p.Ser354=
c.1062T>C · rs913717970 · VCV1083512
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0367%, amr)
Conditions
1
Cardiovascular phenotype
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 0.18 | GERP -1.3 |
| Overall | ||
| CADD | 7.66 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0367%
Admixed American · 22/59,990 alleles
Filtering AF
0.0248%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0209%
Overall
0.00155%
25/1,613,972 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0367% | 2,727 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,827 |
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.Ser354=
- Coding
- c.1062T>C
- MANE Select
- NM_000237
- dbSNP
- rs913717970
- Type
- single nucleotide variant
- Location
- chr8:19959303 (GRCh38)
- Gene constraint
- LOEUF 1.075 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.36 · 5 PDB
- Residue 354
- the plat domain
Similar variants
- LPL p.Ser354Gly Uncertain significance ★ ⚠ same residue
- LPL c.1019-2A>T Pathogenic ★★ same condition
- LPL c.1139+1G>A Likely pathogenic ★★ same condition
- LPL c.1322+1G>C Pathogenic/Likely pathogenic ★★ same condition
- LPL c.249+1G>A Pathogenic ★★ same condition
- LPL p.Ala98Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
- LPL p.Arg197Cys Likely pathogenic ★★ same condition
- LPL p.Asp277Asn 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-ser354 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown