LRP6 p.Lys76=
c.228A>G · rs757453495 · VCV2991953
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0133%, amr)
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 0.55 | GERP -0.73, phastCons 1 |
| Overall | ||
| CADD | 2.605 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0133%
Admixed American · 8/60,004 alleles
Filtering AF
0.00661%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00482%
Overall
0.00124%
20/1,614,098 alleles · ultra-rare
exomes 18/1,461,894 · genomes 2/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0133% | 7,501 |
| European (non-Finnish) | 0.00102% | 98,337 |
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.Lys76=
- Coding
- c.228A>G
- MANE Select
- NM_002336
- dbSNP
- rs757453495
- Type
- single nucleotide variant
- Location
- chr12:12244483 (GRCh38)
- Gene constraint
- LOEUF 0.27 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 79.87 · 30 PDB
- Residue 76
- a β-strand; the 'beta-propeller 1' region
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-lys76 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown