LRP5 p.Pro1496=
c.4488G>A · rs1565118560 · VCV635003
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000174%, nfe)
Conditions
1
exudative vitreoretinopathy 4
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.312 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.41 | donor loss · deltas |
| Pangolin | Δ0.45 | loss · gain 0.09 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 1.5 | phastCons 1 |
| Overall | ||
| CADD | 22.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000174%
European (non-Finnish) · 2/1,147,544 alleles
Filtering AF
2.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000129%
2/1,548,148 alleles · very rare
exomes 2/1,396,058 · genomes 0/152,090 · 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.Pro1496=
- Coding
- c.4488G>A
- MANE Select
- NM_002335
- dbSNP
- rs1565118560
- Type
- single nucleotide variant
- Location
- chr11:68439916 (GRCh38)
- Gene constraint
- LOEUF 0.482 · pLI 0.94 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.65
- Residue 1496
- the 'disordered' region
Similar variants
- LRP5 p.Pro1496Leu Uncertain significance ★★ ⚠ same residue
- LRP5 c.3236+2T>G Pathogenic/Likely pathogenic ★★ same condition
- LRP5 c.4488+2T>G Pathogenic/Likely pathogenic ★★ same condition
- LRP5 p.Ala422Thr Likely pathogenic ★★ same condition
- LRP5 p.Arg428Ter Pathogenic ★★ same condition
- LRP5 p.Arg494Gln Pathogenic/Likely pathogenic ★★ same condition
- LRP5 p.Asn198Ser Pathogenic/Likely pathogenic ★★ same condition
- LRP5 p.Asp424Asn Pathogenic/Likely pathogenic ★★ 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/lrp5-p-pro1496 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown