Is LPL p.Ala28Val (c.83C>T) pathogenic?

LPL p.Ala28Val (c.83C>T) is classified Uncertain significance in LPL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-19). AlphaMissense: likely benign (0.0892); Ultra-rare (popmax 0.0605%, eas); Associated with Cardiovascular phenotype.

What condition is associated with LPL p.Ala28Val (c.83C>T)?

LPL p.Ala28Val (c.83C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is LPL p.Ala28Val (c.83C>T) in the general population?

LPL p.Ala28Val (c.83C>T) is ultra-rare (popmax 0.0605%, eas) (gnomAD).

What do computational predictors say about LPL p.Ala28Val (c.83C>T)?

AlphaMissense predicts likely benign (score 0.0892) — an in-silico prediction, not a clinical call.

LPL p.Ala28Val

c.83C>T · VCV3539206

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0892 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0605%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0892	likely benign
REVEL	0.289	benign-leaning
SaProt	LLR -6.91	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -1.7, phastCons 0.69
Regional constraint	o/e 1.09	unconstrained · MANE · 23 kb · p 0.027 · regional, not allelic
Overall
CADD	14.59	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0605% East Asian · 27/44,624 alleles

Filtering AF 0.0426% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0367%

Overall 0.00186% 27/1,455,274 alleles · ultra-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.Ala28Val
Coding: c.83C>T
MANE Select: NM_000237
Type: single nucleotide variant
Location: chr8:19939523 (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.Ala28= Likely benign ★★ same residue
LPL p.Ala28Asp Uncertain significance ★ ⚠ 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-ala28val (accessed [today's date]).

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