LRP5 p.Ser192=
c.576G>A · rs139063572 · VCV860778
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.113%, afr)
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 -20 | GERP -9.7 |
| Overall | ||
| CADD | 1.088 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.113%
African / African-American · 85/75,050 alleles
Filtering AF
0.0938%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0866%
Overall
0.00582%
94/1,614,116 alleles · rare
exomes 60/1,461,784 · genomes 34/152,332 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.113% | 883 |
| Admixed American | 0.00666% | 15,006 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,252 |
| European (non-Finnish) | 0.000254% | 393,332 |
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.Ser192=
- Coding
- c.576G>A
- MANE Select
- NM_002335
- dbSNP
- rs139063572
- Type
- single nucleotide variant
- Location
- chr11:68357737 (GRCh38)
- Gene constraint
- LOEUF 0.482 · pLI 0.94 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.65
- Residue 192
- the 'beta-propeller 1' region
Similar variants
- LRP5 p.Ser192Leu Uncertain significance ★★ ⚠ same residue
- LRP5 p.Ser192Trp Uncertain significance ★ ⚠ 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
- LRP5 p.Ala214Thr 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-ser192 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown