LPL p.Arg214Ser
c.642A>C · VCV4853457
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.6291 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.6291 | likely pathogenic |
|---|---|---|
| REVEL | 0.653 | pathogenic-leaning |
| SaProt | LLR -2.02 | tolerated |
| ⇒ AlphaMissense and REVEL call this damaging; SaProt does not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.51 | GERP -5.5, phastCons 0.81 |
| Regional constraint | o/e 1.09 | unconstrained · MANE · 23 kb · p 0.027 · regional, not allelic |
| Overall | ||
| CADD | 21.7 | 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.Arg214Ser
- Coding
- c.642A>C
- MANE Select
- NM_000237
- Type
- single nucleotide variant
- Location
- chr8:19954220 (GRCh38)
- Gene constraint
- LOEUF 1.075 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.36 · 5 PDB
Similar variants
- LPL p.Arg214Ile Uncertain significance ★★ ⚠ same residue
- LPL p.Arg214Ter 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
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-arg214ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown