PCSK9 p.Val285=
c.855G>A · rs2100311818 · VCV1332071
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 8.5e-05%, nfe)
Conditions
1
familial hypercholesterolemia
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 -0.059 | GERP 0.89, phastCons 0.77 |
| Overall | ||
| CADD | 2.308 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.5e-05%
European (non-Finnish) · 1/1,177,002 alleles
Overall
6.86e-05%
1/1,456,860 alleles · very rare
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
- PCSK9
- Protein
- p.Val285=
- Coding
- c.855G>A
- MANE Select
- NM_174936
- dbSNP
- rs2100311818
- Type
- single nucleotide variant
- Location
- chr1:55056048 (GRCh38)
- Gene constraint
- LOEUF 1.25 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
- Structure
- AlphaFold pLDDT 85.03 · 66 PDB
- Residue 285
- a β-strand; the peptidase s8 domain
Similar variants
- PCSK9 p.Val285Met Uncertain significance ★ ⚠ same residue
- PCSK9 p.Val285Ala Uncertain significance ★★ ⚠ same residue
- PCSK9 p.Arg215His Pathogenic/Likely pathogenic ★★ ⚠ same condition
- PCSK9 p.Asp374His Pathogenic/Likely pathogenic ★★ ⚠ same condition
- PCSK9 p.Asp374Tyr Pathogenic/Likely pathogenic ★★ ⚠ same condition
- PCSK9 c.1863+1G>A Uncertain significance ★★ same condition
- PCSK9 c.1864-12G>A Uncertain significance ★★ same condition
- PCSK9 c.207+5G>A Uncertain significance ★★ 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/pcsk9-p-val285 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown