Is LRP1 p.Pro3734= (c.11202C>G) pathogenic?

LRP1 p.Pro3734= (c.11202C>G) is classified Likely benign in LRP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-26). Ultra-rare (popmax 0.012%, afr); Associated with LRP1-related disorder.

What condition is associated with LRP1 p.Pro3734= (c.11202C>G)?

LRP1 p.Pro3734= (c.11202C>G) is associated with LRP1-related disorder (ClinVar).

How common is LRP1 p.Pro3734= (c.11202C>G) in the general population?

LRP1 p.Pro3734= (c.11202C>G) is ultra-rare (popmax 0.012%, afr) (gnomAD).

LRP1 p.Pro3734=

c.11202C>G · rs749898308 · VCV3036034

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Conditions

LRP1-related disorder

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 0.68	GERP -0.37, phastCons 1
Overall
CADD	4.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% African / African-American · 9/74,926 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.000682% 11/1,613,320 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,325
Remaining individualsnot grpmax-eligible	0.0016%	62,466
European (non-Finnish)	8.48e-05%	1,179,711

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: LRP1
Protein: p.Pro3734=
Coding: c.11202C>G
MANE Select: NM_173177 · reported on NM_002332
dbSNP: rs749898308
Type: single nucleotide variant
Location: chr12:57205116 (GRCh38)
Structure: AlphaFold pLDDT 88.37

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

Disease context

LRP1-related disorder

Similar variants

LRP1 c.10346-2A>T Likely pathogenic ★ same condition
LRP1 p.Pro1029Ser Uncertain significance ★ same condition
LRP1 p.Glu2536Lys Uncertain significance same condition
LRP1 c.10225+8G>A Likely benign same condition
LRP1 c.10595-9C>T Likely benign same condition
LRP1 c.1228-7G>A Likely benign same condition
LRP1 c.4606+8G>T Likely benign same condition
LRP1 c.67+3G>A Likely benign 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/lrp1-p-pro3734 (accessed [today's date]).

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