LRP5 p.Ser246=
c.738C>T · rs768638466 · VCV284331
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.394%, mid)
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 Δ0.41 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -15 | GERP -3.9 |
| Overall | ||
| CADD | 3.157 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.394%
Middle Eastern · 24/6,084 alleles
Filtering AF
0.272%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.232%
Overall
0.00267%
43/1,612,948 alleles · rare
exomes 39/1,461,186 · genomes 4/151,762 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.394% | 254 |
| Admixed American | 0.00667% | 14,989 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,478 |
| African / African-American | 0.00134% | 74,784 |
| European (non-Finnish) | 0.0011% | 90,761 |
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.Ser246=
- Coding
- c.738C>T
- MANE Select
- NM_002335
- dbSNP
- rs768638466
- Type
- single nucleotide variant
- Location
- chr11:68363798 (GRCh38)
- Gene constraint
- LOEUF 0.482 · pLI 0.94 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.65
- Residue 246
- the 'beta-propeller 1' 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-ser246 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown