LRP2 p.Arg3586=
c.10758T>C · rs1390824988 · VCV2881507
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00446%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.9 | GERP -4.2 |
| Overall | ||
| CADD | 0.06 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00446%
East Asian · 2/44,882 alleles
Filtering AF
0.000739%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000366%
Overall
0.000867%
14/1,614,122 alleles · very rare
exomes 13/1,461,804 · genomes 1/152,318 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00446% | 22,441 |
| South Asian | 0.0011% | 91,084 |
| European (non-Finnish) | 0.000932% | 107,271 |
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
- LRP2
- Protein
- p.Arg3586=
- Coding
- c.10758T>C
- MANE Select
- NM_004525
- dbSNP
- rs1390824988
- Type
- single nucleotide variant
- Location
- chr2:169175203 (GRCh38)
- Gene constraint
- LOEUF 0.352 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 3586
- the ldl-receptor class a 27 domain; an α-helix
Similar variants
- LRP2 p.Arg3586Cys Uncertain significance ★ same residue
- LRP2 p.Arg3586His Conflicting classifications of pathogenicity ★ ⚠ same residue
- LRP2 c.12019+1G>A Likely pathogenic ★★ same type
- LRP2 c.2639+1G>A Pathogenic/Likely pathogenic ★★ same type
- LRP2 c.3667+1G>A Pathogenic/Likely pathogenic ★★ same type
- LRP2 c.8452+1G>A Pathogenic ★★ same type
- LRP2 p.Arg1953Ter Pathogenic/Likely pathogenic ★★ same type
- LRP2 p.Arg2095Ter Pathogenic/Likely pathogenic ★★ 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/lrp2-p-arg3586 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown