Is APOE p.Arg163Pro (c.488G>C) pathogenic?

APOE p.Arg163Pro (c.488G>C) is classified Pathogenic in APOE (ClinVar, No assertion criteria, 1 submitter; last evaluated 2000-10-06). AlphaMissense: likely pathogenic (0.8019); Absent from gnomAD v4.1; Associated with lipoprotein glomerulopathy.

What condition is associated with APOE p.Arg163Pro (c.488G>C)?

APOE p.Arg163Pro (c.488G>C) is associated with lipoprotein glomerulopathy (ClinVar).

How common is APOE p.Arg163Pro (c.488G>C) in the general population?

APOE p.Arg163Pro (c.488G>C) is absent from gnomAD v4.1 (gnomAD).

How is Lipoprotein glomerulopathy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about APOE p.Arg163Pro (c.488G>C)?

AlphaMissense predicts likely pathogenic (score 0.8019) — an in-silico prediction, not a clinical call.

APOE p.Arg163Pro

c.488G>C · rs121918397 · VCV17879

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8019 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,557,696)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

lipoprotein glomerulopathy

Computational evidence

Protein change
AlphaMissense	0.8019	likely pathogenic ✓ concordant with ClinVar · top 4% in APOE
REVEL	0.697	pathogenic-leaning
SaProt	LLR -12.00	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 1.7, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 2,622 bp · p 0.6 · regional, not allelic
Overall
CADD	24.8	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

No allele count reported in gnomAD v4.1 (AN 1,557,696). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: APOE
Protein: p.Arg163Pro
Coding: c.488G>C
MANE Select: NM_000041
dbSNP: rs121918397
Type: single nucleotide variant
Location: chr19:44908784 (GRCh38)
Gene constraint: LOEUF 1.319 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.13 · 31 PDB
Residue 163: the '8 x 22 aa approximate tandem repeats' region; the 'ldl and other lipoprotein receptors binding' region; a binding site; a UniProt-annotated variant site (in hlpp3; also found in a patient with hypercholesterolemia; apoe4 philadelphia and apoe2-type); a UniProt-annotated variant site (in hlpp3; uncertain significance; apoe kochi); a UniProt-annotated variant site (in lpg; apoe2 sendai; decreased binding to ldl receptor; induces intraglomerular deposition of apoe-containing lipoproteins); an α-helix

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

Disease context

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

For Lipoprotein glomerulopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood, Elderly
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

APOE p.Arg163His Conflicting classifications of pathogenicity ★ ⚠ same residue
APOE p.Arg163Leu Uncertain significance ★ ⚠ same residue
APOE p.Arg163Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
APOE p.Arg163= Likely benign ★ same residue
APOE p.Arg43Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
APOE p.Arg269Gly Uncertain significance ★★ ⚠ same condition
APOE p.Glu230Lys Uncertain significance ★★ ⚠ same condition
APOE p.Gly145Asp Uncertain significance ★★ 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/apoe-p-arg163pro (accessed [today's date]).

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