LRP5 p.Val599=
c.1797C>T · rs554437931 · VCV1102519
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0198%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.62 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.1 | GERP -3.1 |
| Overall | ||
| CADD | 5.983 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0198%
South Asian · 18/91,032 alleles
Filtering AF
0.0127%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0106%
Overall
0.0013%
21/1,613,470 alleles · ultra-rare
exomes 17/1,461,186 · genomes 4/152,284 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0198% | 5,057 |
| African / African-American | 0.00133% | 75,022 |
| European (non-Finnish) | 0.000169% | 590,012 |
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.Val599=
- Coding
- c.1797C>T
- MANE Select
- NM_002335
- dbSNP
- rs554437931
- Type
- single nucleotide variant
- Location
- chr11:68403695 (GRCh38)
- Gene constraint
- LOEUF 0.482 · pLI 0.94 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.65
- Residue 599
- the 'beta-propeller 2' region
Similar variants
- 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
- LRP5 p.Ala214Thr Pathogenic ★★ same type
- LRP5 p.Ala242Thr Pathogenic/Likely pathogenic ★★ same type
- LRP5 p.Ala422Ser 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-val599 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown