PRNP p.Val161=
c.483G>A · rs746526977 · VCV1335458
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000678%, 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 1.4 | GERP -0.36, phastCons 1 |
| Overall | ||
| CADD | 3.52 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000678%
European (non-Finnish) · 8/1,180,018 alleles
Filtering AF
0.000292%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000211%
Overall
0.000496%
8/1,613,930 alleles · very rare
exomes 7/1,461,894 · genomes 1/152,036 · 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
- PRNP
- Protein
- p.Val161=
- Coding
- c.483G>A
- MANE Select
- NM_000311
- dbSNP
- rs746526977
- Type
- single nucleotide variant
- Location
- chr20:4699703 (GRCh38)
- Gene constraint
- LOEUF 1.036 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.18 · 70 PDB
- Residue 161
- a β-strand; the 'interaction with grb2, eri3 and syn1' region
Similar variants
- PRNP p.Ala117Val Pathogenic ★★ ⚠ same type
- PRNP p.Arg148His Likely pathogenic ★★ ⚠ same type
- PRNP p.Arg208His Pathogenic/Likely pathogenic ★★ ⚠ same type
- PRNP p.Asp178Asn Pathogenic/Likely pathogenic ★★ ⚠ same type
- PRNP p.Gln217Arg Likely pathogenic ★★ ⚠ same type
- PRNP p.Glu200Lys Pathogenic ★★ ⚠ same type
- PRNP p.Gly131Val Pathogenic/Likely pathogenic ★★ same type
- PRNP p.Phe198Ser Pathogenic ★★ ⚠ 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/prnp-p-val161 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown