LDLR p.Ile451=
c.1353C>T · VCV4859171
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Conditions
1
Cardiovascular phenotype
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 1.4 | GERP -0.7, phastCons 1 |
| Overall | ||
| CADD | 10.83 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,876 alleles
Overall
6.2e-05%
1/1,613,964 alleles · very rare
exomes 1/1,461,660 · genomes 0/152,304 · 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.Ile451=
- Coding
- c.1353C>T
- MANE Select
- NM_000527
- Type
- single nucleotide variant
- Location
- chr19:11113444 (GRCh38)
- Gene constraint
- LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.81 · 36 PDB
- Residue 451
- a UniProt-annotated variant site (in fhcl1); a β-strand
Similar variants
- LDLR p.Ile451Phe Likely pathogenic ★★ same residue
- LDLR p.Ile451Thr Pathogenic/Likely pathogenic ★★ same residue
- LDLR p.Ile451Met Uncertain significance ★ ⚠ same residue
- LDLR p.Ile451Val Uncertain significance ★ ⚠ same residue
- LDLR c.1061-1G>C Pathogenic/Likely pathogenic ★★ same condition
- LDLR c.1186+1G>T Pathogenic ★★ same condition
- LDLR c.1186+2T>G Pathogenic/Likely pathogenic ★★ same condition
- LDLR c.1586+1G>A Pathogenic/Likely 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-ile451 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown