Is LPL p.Lys331Glu (c.991A>G) pathogenic?

LPL p.Lys331Glu (c.991A>G) is classified Pathogenic/Likely pathogenic in LPL (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-27). AlphaMissense: likely pathogenic (0.6805); Absent from gnomAD v4.1; Associated with LPL-related disorder.

What condition is associated with LPL p.Lys331Glu (c.991A>G)?

LPL p.Lys331Glu (c.991A>G) is associated with LPL-related disorder, familial lipoprotein lipase deficiency, lipase deficiency, combined (ClinVar).

How common is LPL p.Lys331Glu (c.991A>G) in the general population?

LPL p.Lys331Glu (c.991A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LPL p.Lys331Glu (c.991A>G)?

AlphaMissense predicts likely pathogenic (score 0.6805) — an in-silico prediction, not a clinical call.

LPL p.Lys331Glu

c.991A>G · rs2069982771 · VCV1030690

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.6805 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

LPL-related disorder

Computational evidence

Protein change
AlphaMissense	0.6805	likely pathogenic ✓ concordant with ClinVar
REVEL	0.532	indeterminate
SaProt	LLR -7.67	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.7, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 23 kb · p 0.027 · regional, not allelic
Overall
CADD	24.3	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.Lys331Glu
Coding: c.991A>G
MANE Select: NM_000237
dbSNP: rs2069982771
Type: single nucleotide variant
Location: chr8:19956056 (GRCh38)
Gene constraint: LOEUF 1.075 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.36 · 5 PDB

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

Disease context

LPL-related disorder

Also linked: familial lipoprotein lipase deficiency lipase deficiency, combined

Similar variants

LPL p.Lys331= Likely benign ★ 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-lys331glu (accessed [today's date]).

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