Is LPL p.Arg309fs (c.925del) pathogenic?

LPL p.Arg309fs (c.925del) is classified Pathogenic in LPL (ClinVar, No assertion criteria, 1 submitter). Absent from gnomAD; Associated with familial lipoprotein lipase deficiency.

What condition is associated with LPL p.Arg309fs (c.925del)?

LPL p.Arg309fs (c.925del) is associated with familial lipoprotein lipase deficiency (ClinVar).

How common is LPL p.Arg309fs (c.925del) in the general population?

LPL p.Arg309fs (c.925del) is absent from gnomAD (gnomAD).

LPL p.Arg309fs

c.925del · rs2540107223 · VCV2429741

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

familial lipoprotein lipase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.4	GERP 2.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: LPL
Protein: p.Arg309fs
Coding: c.925del
MANE Select: NM_000237
dbSNP: rs2540107223
Type: Deletion
Location: chr8:19955989 (GRCh38)
Gene constraint: LOEUF 1.075 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.36 · 5 PDB
Residue 309: a β-strand; a disulfide bond

Full LPL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial lipoprotein lipase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LPL p.Val230fs Pathogenic/Likely pathogenic ★★ same condition
LPL p.Arg309Cys Uncertain significance ★★ ⚠ same residue
LPL p.Ala458fs Likely pathogenic ★ same condition
LPL p.Cys266fs Likely pathogenic ★ same condition
LPL p.Trp113fs Likely pathogenic ★ same condition
LPL p.Ala248fs Pathogenic same condition
LPL c.1019-2A>T Pathogenic ★★ same condition
LPL c.1019-3C>A 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-arg309fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown