LPL p.Ser286Arg
c.858T>G · VCV3691103
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9736 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9736 | likely pathogenic ✓ concordant with ClinVar |
|---|---|---|
| REVEL | 0.699 | pathogenic-leaning |
| SaProt | LLR -9.22 | tolerated |
| ⇒ AlphaMissense and REVEL call this damaging; SaProt does not. | ||
| Splicing | ||
| SpliceAI | Δ0.47 | donor loss · deltas |
| Constraint at this position | ||
| Conservation | phyloP -1.5 | GERP -5.4 |
| Regional constraint | o/e 1.09 | unconstrained · MANE · 23 kb · p 0.027 · regional, not allelic |
| Overall | ||
| CADD | 21.3 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- LPL
- Protein
- p.Ser286Arg
- Coding
- c.858T>G
- MANE Select
- NM_000237
- Type
- single nucleotide variant
- Location
- chr8:19955923 (GRCh38)
- Gene constraint
- LOEUF 1.075 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.36 · 5 PDB
- Residue 286
- a UniProt-annotated variant site (in hlpp1)
Similar variants
- LPL p.Ser286Gly Likely pathogenic ★★ ⚠ 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
- LPL c.89-1G>A Pathogenic/Likely 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-ser286arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown