Is LRP2 p.Arg3148Pro (c.9443G>C) pathogenic?

LRP2 p.Arg3148Pro (c.9443G>C) is classified Uncertain significance in LRP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). AlphaMissense: likely pathogenic (0.8509); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with LRP2 p.Arg3148Pro (c.9443G>C)?

LRP2 p.Arg3148Pro (c.9443G>C) is associated with Inborn genetic diseases (ClinVar).

How common is LRP2 p.Arg3148Pro (c.9443G>C) in the general population?

LRP2 p.Arg3148Pro (c.9443G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LRP2 p.Arg3148Pro (c.9443G>C)?

AlphaMissense predicts likely pathogenic (score 0.8509) — an in-silico prediction, not a clinical call.

LRP2 p.Arg3148Pro

c.9443G>C · VCV4048707

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8509 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8509	likely pathogenic
REVEL	0.505	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.77	GERP 2.4, phastCons 0.24
Regional constraint	o/e 0.83	unconstrained · MANE · 30 kb · p 2.4e-10 · regional, not allelic
Overall
CADD	20.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LRP2
Protein: p.Arg3148Pro
Coding: c.9443G>C
MANE Select: NM_004525
Type: single nucleotide variant
Location: chr2:169185905 (GRCh38)
Gene constraint: LOEUF 0.352 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3148: the egf-like 3 domain

Full LRP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LRP2 p.Arg3148= Conflicting classifications of pathogenicity ★ same residue
LRP2 p.Arg3148Gln Uncertain significance ★ same residue
LRP2 c.5227+6G>C Uncertain significance ★★ same condition
LRP2 p.Ala1007Val Uncertain significance ★★ ⚠ same condition
LRP2 p.Ala1071Val Uncertain significance ★★ same condition
LRP2 p.Ala1105Pro Uncertain significance ★★ ⚠ same condition
LRP2 p.Ala1265Val Uncertain significance ★★ ⚠ same condition
LRP2 p.Ala1493Val 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/lrp2-p-arg3148pro (accessed [today's date]).

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