LRP6 p.Asp289=
c.867C>T · rs201730937 · VCV2202301
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.185%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.33 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 7 | GERP 1.5, phastCons 1 |
| Overall | ||
| CADD | 16.43 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.185%
East Asian · 83/44,846 alleles
Filtering AF
0.153%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.141%
Overall
0.00539%
87/1,613,450 alleles · rare
exomes 77/1,461,128 · genomes 10/152,322 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.185% | 540 |
| Middle Eastern | 0.0165% | 6,060 |
| Admixed American | 0.00167% | 60,030 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
| European (non-Finnish) | 8.48e-05% | 1,179,434 |
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
- LRP6
- Protein
- p.Asp289=
- Coding
- c.867C>T
- MANE Select
- NM_002336
- dbSNP
- rs201730937
- Type
- single nucleotide variant
- Location
- chr12:12184089 (GRCh38)
- Gene constraint
- LOEUF 0.27 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 79.87 · 30 PDB
- Residue 289
- the egf-like 1 domain; a turn
Similar variants
- LRP6 c.3207-2A>G Likely pathogenic ★★ same type
- LRP6 p.Arg335Ter Pathogenic/Likely pathogenic ★★ same type
- LRP6 p.Arg415Ter Pathogenic/Likely pathogenic ★★ same type
- LRP6 p.Arg585Ter Pathogenic/Likely pathogenic ★★ same type
- LRP6 p.Arg644Ter Pathogenic ★★ same type
- LRP6 p.Arg728Ter Pathogenic ★★ same type
- LRP6 p.Arg990Ter Pathogenic ★★ same type
- LRP6 p.Ala1304Thr Uncertain significance ★★ ⚠ 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/lrp6-p-asp289 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown