VLDLR p.Pro105=
c.315A>G · rs138500615 · VCV212558
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0153%, nfe)
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 -1.2 | GERP -4 |
| Overall | ||
| CADD | 1.482 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0153%
European (non-Finnish) · 181/1,180,048 alleles
Filtering AF
0.0135%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0128%
Overall
0.0116%
187/1,614,128 alleles · ultra-rare
exomes 173/1,461,888 · genomes 14/152,240 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0153% | 6,520 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| African / African-American | 0.004% | 24,980 |
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
- VLDLR
- Protein
- p.Pro105=
- Coding
- c.315A>G
- MANE Select
- NM_003383
- dbSNP
- rs138500615
- Type
- single nucleotide variant
- Location
- chr9:2639971 (GRCh38)
- Gene constraint
- LOEUF 0.828 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.12 · 27 PDB
- Residue 105
- a turn; the ldl-receptor class a 2 domain
Similar variants
- VLDLR c.2252-2A>C Likely pathogenic ★★ same type
- VLDLR c.449-2A>T Likely pathogenic ★★ same type
- VLDLR c.83-1G>A Pathogenic/Likely pathogenic ★★ same type
- VLDLR p.Arg279Ter Pathogenic ★★ same type
- VLDLR p.Arg301Ter Pathogenic ★★ same type
- VLDLR p.Trp529Ter Pathogenic ★★ same type
- VLDLR c.-154C>G Uncertain significance ★★ same type
- VLDLR c.-392C>T Uncertain significance ★★ 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/vldlr-p-pro105 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown