Is LPL p.Phe41fs (c.120dup) pathogenic?

LPL p.Phe41fs (c.120dup) is classified Likely pathogenic in LPL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). Associated with familial lipoprotein lipase deficiency.

What condition is associated with LPL p.Phe41fs (c.120dup)?

LPL p.Phe41fs (c.120dup) is associated with familial lipoprotein lipase deficiency (ClinVar).

LPL p.Phe41fs

c.120dup · VCV4070188

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 2 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.2	GERP -4.8, phastCons 0.99

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

Variant & gene context

Gene: LPL
Protein: p.Phe41fs
Coding: c.120dup
MANE Select: NM_000237
Type: Duplication
Location: chr8:19948208 (GRCh38)
Gene constraint: LOEUF 1.075 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.36 · 5 PDB
Residue 41: a β-strand; the 'interaction with gpihbp1' region

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.Asn308delinsGlySerAlaTer Pathogenic ★★ same condition
LPL c.250dup Likely pathogenic ★ same condition
LPL p.Gln224fs Likely pathogenic ★ same condition
LPL p.Phe41= Likely benign ★ same residue
LPL c.898_1019-1234dup Pathogenic same condition
LPL c.1019-2A>T Pathogenic ★★ same condition
LPL c.1019-3C>A Pathogenic/Likely pathogenic ★★ same condition
LPL c.1139+1G>A 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-phe41fs (accessed [today's date]).

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