Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 11 submitters
gnomAD v4.1
Common
common (popmax 97.7%, eas) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -13 | GERP -3.9 |
| Overall | ||
| CADD | 2.157 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
97.7%
East Asian · 43,842/44,870 alleles
Filtering AF
96.9%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 96.6%
Overall
90.2%
1,455,493/1,614,072 alleles · common
exomes 1,327,694/1,461,830 · genomes 127,799/152,242 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 97.7% | 1 |
| Finnishnot grpmax-eligible | 96.4% | 1 |
| Amishnot grpmax-eligible | 92.4% | 1 |
| Admixed American | 92.1% | 1 |
| South Asian | 92.1% | 1 |
| European (non-Finnish) | 91.1% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 89.2% | 1 |
| Remaining individualsnot grpmax-eligible | 89.1% | 1 |
| Middle Eastern | 85.4% | 1 |
| African / African-American | 63% | 2 |
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.Phe549=
- Coding
- c.1647T>C
- MANE Select
- NM_002335
- dbSNP
- rs545382
- Type
- single nucleotide variant
- Location
- chr11:68403545 (GRCh38)
- Gene constraint
- LOEUF 0.482 · pLI 0.94 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.65
- Residue 549
- the 'beta-propeller 2' 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-phe549 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown