LRP6 p.Phe702=
c.2106C>T · VCV4915662
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.016%, 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 -2.9 | GERP -3.7 |
| Overall | ||
| CADD | 1.402 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.016%
African / African-American · 12/74,896 alleles
Filtering AF
0.00922%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00722%
Overall
0.00452%
73/1,614,008 alleles · ultra-rare
exomes 58/1,461,884 · genomes 15/152,124 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.016% | 6,241 |
| Admixed American | 0.005% | 20,000 |
| European (non-Finnish) | 0.00449% | 22,265 |
| East Asian | 0.00446% | 22,441 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,243 |
| South Asian | 0.0011% | 91,078 |
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.Phe702=
- Coding
- c.2106C>T
- MANE Select
- NM_002336
- Type
- single nucleotide variant
- Location
- chr12:12162366 (GRCh38)
- Gene constraint
- LOEUF 0.27 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 79.87 · 30 PDB
- Residue 702
- the 'beta-propeller 3' region; a UniProt-annotated variant site (in sthag7; pathogenic; loss of function in wnt signaling)
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-phe702 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown