Is LPL p.Arg32fs (c.94_98del) pathogenic?

LPL p.Arg32fs (c.9498del) is classified Pathogenic in LPL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-29). Very rare (popmax 8.47e-05%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with LPL p.Arg32fs (c.94_98del)?

LPL p.Arg32fs (c.94_98del) is associated with Cardiovascular phenotype (ClinVar).

How common is LPL p.Arg32fs (c.94_98del) in the general population?

LPL p.Arg32fs (c.94_98del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

LPL p.Arg32fs

c.94_98del · rs1263698980 · VCV950321

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Cardiovascular phenotype

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 3.1	GERP -5.1, phastCons 0.97

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,960 alleles

Overall 0.000137% 2/1,461,818 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)grpmax	8.47e-05%	1,179,960

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg32fs
Coding: c.94_98del
MANE Select: NM_000237
dbSNP: rs1263698980
Type: Deletion
Location: chr8:19948182 (GRCh38)
Gene constraint: LOEUF 1.075 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.36 · 5 PDB
Residue 32: an α-helix; the 'interaction with gpihbp1' region

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LPL p.Asn147fs Pathogenic ★★ same condition
LPL p.Asn188_Phe189insTer Pathogenic ★★ same condition
LPL c.-5_-4del Uncertain significance ★ same condition
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

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-arg32fs (accessed [today's date]).

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