LRP5 p.Arg1237=
c.3711G>A · rs1442600085 · VCV2875808
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00195%, nfe)
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 -0.55 | GERP -5.1, phastCons 0.002 |
| Overall | ||
| CADD | 5.728 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00195%
European (non-Finnish) · 23/1,180,044 alleles
Filtering AF
0.0013%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00108%
Overall
0.00142%
23/1,614,190 alleles · very rare
exomes 23/1,461,850 · genomes 0/152,340 · joint denominator
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
- LRP5
- Protein
- p.Arg1237=
- Coding
- c.3711G>A
- MANE Select
- NM_002335
- dbSNP
- rs1442600085
- Type
- single nucleotide variant
- Location
- chr11:68429648 (GRCh38)
- Gene constraint
- LOEUF 0.482 · pLI 0.94 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.65
- Residue 1237
- the egf-like 4 domain
Similar variants
- LRP5 p.Arg1237Gln Uncertain significance ★★ ⚠ same residue
- LRP5 p.Arg1237Gly Uncertain significance ★ ⚠ same residue
- LRP5 p.Arg1237Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
- LRP5 c.1412+1G>A Pathogenic ★★ same type
- LRP5 c.2827+1G>A Pathogenic ★★ same type
- LRP5 c.3236+2T>G Pathogenic/Likely pathogenic ★★ same type
- LRP5 c.4488+2T>G Pathogenic/Likely pathogenic ★★ same type
- LRP5 c.884-2A>G 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/lrp5-p-arg1237 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown