Is LRP1 p.Arg46Pro (c.137G>C) pathogenic?

LRP1 p.Arg46Pro (c.137G>C) is classified Uncertain significance in LRP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-27). AlphaMissense: likely pathogenic (0.9842); Absent from gnomAD v4.1.

How common is LRP1 p.Arg46Pro (c.137G>C) in the general population?

LRP1 p.Arg46Pro (c.137G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LRP1 p.Arg46Pro (c.137G>C)?

AlphaMissense predicts likely pathogenic (score 0.9842) — an in-silico prediction, not a clinical call.

LRP1 p.Arg46Pro

c.137G>C · rs146149784 · VCV3120109

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9842 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.9842	likely pathogenic · top 4% in LRP1
REVEL	0.528	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Overall
CADD	27.4	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: LRP1
Protein: p.Arg46Pro
Coding: c.137G>C
MANE Select: NM_173177 · reported on NM_002332
dbSNP: rs146149784
Type: single nucleotide variant
Location: chr12:57138528 (GRCh38)
Structure: AlphaFold pLDDT 88.37
Residue 46: the 'required for transcriptional repression' region

Full LRP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LRP1 p.Arg46Gln Uncertain significance ★ ⚠ same residue
LRP1 p.Ala1564Thr Uncertain significance ★★ same type
LRP1 p.Arg228Gln Uncertain significance ★★ same type
LRP1 p.Arg2440Trp Uncertain significance ★★ ⚠ same type
LRP1 p.Arg539Gln Uncertain significance ★★ same type
LRP1 p.Asp4483Tyr Uncertain significance ★★ same type
LRP1 p.Ser2907Pro Uncertain significance ★★ same type
LRP1 p.Val3296Ile Uncertain significance ★★ ⚠ same type

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/lrp1-p-arg46pro (accessed [today's date]).

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