VLDLR p.Cys97=
c.291C>T · rs750584489 · VCV3012031
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, sas)
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 -0.15 | GERP -0.35, phastCons 0.71 |
| Overall | ||
| CADD | 8.783 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
South Asian · 15/91,076 alleles
Filtering AF
0.0101%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00811%
Overall
0.00291%
47/1,614,170 alleles · ultra-rare
exomes 47/1,461,890 · genomes 0/152,280 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0165% | 6,072 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,836 |
| European (non-Finnish) | 0.00246% | 40,691 |
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.Cys97=
- Coding
- c.291C>T
- MANE Select
- NM_003383
- dbSNP
- rs750584489
- Type
- single nucleotide variant
- Location
- chr9:2639947 (GRCh38)
- Gene constraint
- LOEUF 0.828 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.12 · 27 PDB
- Residue 97
- a β-strand; a disulfide bond; the ldl-receptor class a 2 domain
Similar variants
- VLDLR p.Cys97Ter Pathogenic ★ same residue
- 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
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-cys97 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown