Is LPL p.Ala27= (c.81C>A) pathogenic?

LPL p.Ala27= (c.81C>A) is classified Conflicting classifications of pathogenicity in LPL (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-11-17). Very rare (popmax 0.00696%, nfe); Associated with familial lipoprotein lipase deficiency.

What condition is associated with LPL p.Ala27= (c.81C>A)?

LPL p.Ala27= (c.81C>A) is associated with familial lipoprotein lipase deficiency (ClinVar).

How common is LPL p.Ala27= (c.81C>A) in the general population?

LPL p.Ala27= (c.81C>A) is very rare (popmax 0.00696%, nfe) (gnomAD).

LPL p.Ala27=

c.81C>A · rs764871141 · VCV908633

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00696%, nfe)

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 0.74	GERP 1.3, phastCons 0.87
Overall
CADD	11.38	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00696% European (non-Finnish) · 82/1,177,842 alleles

Filtering AF 0.00572% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00526%

Overall 0.00535% 86/1,607,600 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00696%	14,364
Remaining individualsnot grpmax-eligible	0.00322%	31,077
South Asian	0.00222%	45,125

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.Ala27=
Coding: c.81C>A
MANE Select: NM_000237
dbSNP: rs764871141
Type: single nucleotide variant
Location: chr8:19939521 (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

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

Similar variants

LPL p.Ala27Ser 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-ala27 (accessed [today's date]).

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