Is LPL p.Glu145= (c.435G>A) pathogenic?

LPL p.Glu145= (c.435G>A) is classified Benign/Likely benign in LPL (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 7.5%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with familial lipoprotein lipase deficiency.

What condition is associated with LPL p.Glu145= (c.435G>A)?

LPL p.Glu145= (c.435G>A) is associated with familial lipoprotein lipase deficiency (ClinVar).

LPL p.Glu145=

Q: How common is LPL p.Glu145= (c.435G>A) in the general population?

LPL p.Glu145= (c.435G>A) is common (popmax 7.5%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.435G>A · rs248 · VCV362409

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 7.5%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

familial lipoprotein lipase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -2.1, phastCons 1
Overall
CADD	4.829	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.5% European (non-Finnish) · 87,976/1,173,692 alleles

Filtering AF 7.45% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.44%

Overall 6.53% 105,004/1,607,244 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	7.5%	13
Remaining individualsnot grpmax-eligible	6.26%	16
Finnishnot grpmax-eligible	5.56%	18
African / African-American	4.95%	20
Amishnot grpmax-eligible	3.95%	25
Ashkenazi Jewishnot grpmax-eligible	3.67%	27
Middle Eastern	3.6%	28
South Asian	3.16%	32
Admixed American	2.74%	36
East Asian	0.0112%	8,968

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.Glu145=
Coding: c.435G>A
MANE Select: NM_000237
dbSNP: rs248
Type: single nucleotide variant
Location: chr8:19953315 (GRCh38)
Gene constraint: LOEUF 1.075 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.36 · 5 PDB
Residue 145: an α-helix

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.Glu145Gly Uncertain significance ★ ⚠ same residue
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
LPL c.1139+7A>G Likely pathogenic ★★ same condition
LPL c.249+1G>A Pathogenic ★★ same condition
LPL c.89-1G>A Pathogenic/Likely pathogenic ★★ same condition
LPL c.89-1G>C 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-glu145 (accessed [today's date]).

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