Is LPL p.Ala20= (c.60C>T) pathogenic?

LPL p.Ala20= (c.60C>T) is classified Likely benign in LPL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-07-18). Very rare (popmax 0.00534%, afr); Associated with Cardiovascular phenotype.

What condition is associated with LPL p.Ala20= (c.60C>T)?

LPL p.Ala20= (c.60C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is LPL p.Ala20= (c.60C>T) in the general population?

LPL p.Ala20= (c.60C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

LPL p.Ala20=

c.60C>T · rs1215798253 · VCV1085341

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

Cardiovascular phenotype

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 -0.48	GERP -1.4
Overall
CADD	13.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,904 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00263% 4/152,182 alleles · very rare

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.Ala20=
Coding: c.60C>T
MANE Select: NM_000237
dbSNP: rs1215798253
Type: single nucleotide variant
Location: chr8:19939500 (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

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

Similar variants

LPL p.Ala20fs Pathogenic ★ same residue
LPL p.Ala20Val Likely benign ★ same residue
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
LPL p.Arg197Cys 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-ala20 (accessed [today's date]).

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