LRP2 p.Arg3014=
c.9042G>A · rs376861800 · VCV3018449
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.005%, nfe)
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 -0.77 | GERP -4.8, phastCons 0.006 |
| Overall | ||
| CADD | 4.56 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
European (non-Finnish) · 59/1,180,006 alleles
Filtering AF
0.00394%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00361%
Overall
0.0039%
63/1,613,956 alleles · very rare
exomes 58/1,461,780 · genomes 5/152,176 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.005% | 20,000 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,239 |
| Admixed American | 0.00167% | 60,006 |
| African / African-American | 0.00133% | 74,908 |
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
- LRP2
- Protein
- p.Arg3014=
- Coding
- c.9042G>A
- MANE Select
- NM_004525
- dbSNP
- rs376861800
- Type
- single nucleotide variant
- Location
- chr2:169188256 (GRCh38)
- Gene constraint
- LOEUF 0.352 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 3014
- the ldl-receptor class a 23 domain
Similar variants
- LRP2 p.Arg3014Trp Uncertain significance ★★ same residue
- LRP2 p.Arg3014Gln Uncertain significance ★ same residue
- LRP2 c.12019+1G>A Likely pathogenic ★★ same type
- LRP2 c.2639+1G>A Pathogenic/Likely pathogenic ★★ same type
- LRP2 c.3667+1G>A Pathogenic/Likely pathogenic ★★ same type
- LRP2 c.8452+1G>A Pathogenic ★★ same type
- LRP2 p.Arg1953Ter Pathogenic/Likely pathogenic ★★ same type
- LRP2 p.Arg2095Ter Pathogenic/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/lrp2-p-arg3014 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown