LDLR p.Glu228=
c.684G>A · rs1208216597 · VCV2698636
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 2.4 | GERP -0.72, phastCons 1 |
| Overall | ||
| CADD | 4.749 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,086 |
| African / African-Americangrpmax | 0.00133% | 74,952 |
| European (non-Finnish) | 0.000851% | 117,537 |
Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Glu228=
- Coding
- c.684G>A
- MANE Select
- NM_000527
- dbSNP
- rs1208216597
- Type
- single nucleotide variant
- Location
- chr19:11105590 (GRCh38)
- Gene constraint
- LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.81 · 36 PDB
- Residue 228
- a UniProt-annotated variant site (in chieti-3); a UniProt-annotated variant site (in fhcl1; pathogenic; french canadian-3/mexico; 2% of french canadians); a UniProt-annotated variant site (in fhcl1; tulsa-2); the 'binding to getah virus e1-e2 spike glycoproteins' region; an α-helix; a disulfide bond; the ldl-receptor class a 5 domain
Similar variants
- LDLR p.Glu228Lys Pathogenic ★★★ same residue
- LDLR p.Glu228Asp Pathogenic/Likely pathogenic ★★ same residue
- LDLR p.Glu228Gln Pathogenic/Likely pathogenic ★★ same residue
- LDLR p.Glu228Gly Pathogenic/Likely pathogenic ★★ same residue
- LDLR p.Glu228_Cys231del Pathogenic/Likely pathogenic ★★ same residue
- LDLR p.Glu228Ter Pathogenic ★★ same residue
- LDLR p.Glu228Ala Pathogenic/Likely pathogenic ★★ same residue
- LDLR c.1186+5G>A 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-glu228 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown