LDLR p.Glu408=
c.1224G>A · rs142319510 · VCV1753900
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, nfe)
Conditions
2
Cardiovascular phenotype
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 4.2 | GERP -5.1, phastCons 1 |
| Overall | ||
| CADD | 8.736 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,180,028 alleles
Overall
6.2e-05%
1/1,613,564 alleles · very rare
exomes 1/1,461,486 · genomes 0/152,078 · joint denominator
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
- LDLR
- Protein
- p.Glu408=
- Coding
- c.1224G>A
- MANE Select
- NM_000527
- dbSNP
- rs142319510
- Type
- single nucleotide variant
- Location
- chr19:11113315 (GRCh38)
- Gene constraint
- LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.81 · 36 PDB
- Residue 408
- a UniProt-annotated variant site (in fhcl1; likely pathogenic; algeria-1); a β-strand
Similar variants
- LDLR p.Glu408Lys Likely pathogenic ★★★ same residue
- LDLR p.Glu408Val Likely pathogenic ★★★ same residue
- LDLR p.Glu408Asp Uncertain significance ★★★ ⚠ same residue
- LDLR p.Glu408Gln Uncertain significance ★★★ ⚠ same residue
- LDLR p.Glu408Ter Pathogenic ★ same residue
- LDLR p.Glu408Ala Uncertain significance ★★★ ⚠ same residue
- LDLR c.1186+5G>A Likely pathogenic ★★★ same condition
- LDLR c.1359-1G>A Pathogenic ★★★ same condition
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/ldlr-p-glu408 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown