LRP5 p.Val394=
c.1182G>A · rs746800397 · VCV1543381
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00178%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.33 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.23 | gain · loss 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 3.7 | GERP -0.52, phastCons 1 |
| Overall | ||
| CADD | 15.34 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00178%
European (non-Finnish) · 21/1,180,038 alleles
Filtering AF
0.00114%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000971%
Overall
0.00143%
23/1,613,988 alleles · very rare
exomes 22/1,461,760 · genomes 1/152,228 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00178% | 56,192 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
| Finnishnot grpmax-eligible | 0.00156% | 63,938 |
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.Val394=
- Coding
- c.1182G>A
- MANE Select
- NM_002335
- dbSNP
- rs746800397
- Type
- single nucleotide variant
- Location
- chr11:68386482 (GRCh38)
- Gene constraint
- LOEUF 0.482 · pLI 0.94 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.65
- Residue 394
- the 'beta-propeller 2' region
Similar variants
- LRP5 p.Val394Leu Uncertain significance ★★ ⚠ same residue
- LRP5 p.Val394Met 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-val394 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown