Is LPL p.Ala20Val (c.59C>T) pathogenic?

LPL p.Ala20Val (c.59C>T) is classified Likely benign in LPL (ClinVar, Single submitter, 3 submitters; last evaluated 2026-01-17). AlphaMissense: likely benign (0.1034); Rare (popmax 0.269%, sas); Associated with familial lipoprotein lipase deficiency.

What condition is associated with LPL p.Ala20Val (c.59C>T)?

LPL p.Ala20Val (c.59C>T) is associated with familial lipoprotein lipase deficiency (ClinVar).

How common is LPL p.Ala20Val (c.59C>T) in the general population?

LPL p.Ala20Val (c.59C>T) is rare (popmax 0.269%, sas) (gnomAD).

What do computational predictors say about LPL p.Ala20Val (c.59C>T)?

AlphaMissense predicts likely benign (score 0.1034) — an in-silico prediction, not a clinical call.

LPL p.Ala20Val

c.59C>T · rs572477224 · VCV753489

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1034 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.269%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

familial lipoprotein lipase deficiency

Computational evidence

Protein change
AlphaMissense	0.1034	likely benign
REVEL	0.3	indeterminate
SaProt	LLR -7.19	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.25	GERP 0.75
Regional constraint	o/e 1.09	unconstrained · MANE · 23 kb · p 0.027 · regional, not allelic
Overall
CADD	16.16	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

Grpmax group 0.269% South Asian · 244/90,728 alleles

Filtering AF 0.241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.23%

Overall 0.016% 258/1,610,446 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.269%	372
Middle Eastern	0.0331%	3,025
Remaining individualsnot grpmax-eligible	0.0193%	5,189

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.Ala20Val
Coding: c.59C>T
MANE Select: NM_000237
dbSNP: rs572477224
Type: single nucleotide variant
Location: chr8:19939499 (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.Ala20= 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-ala20val (accessed [today's date]).

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