PRNP p.Pro84=
c.252T>C · rs62637686 · VCV338649
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0357%, afr)
Conditions
1
Inherited prion disease
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 -7.1 | GERP -2.9 |
| Overall | ||
| CADD | 5.358 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0357%
African / African-American · 18/50,448 alleles
Filtering AF
0.023%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.019%
Overall
0.00197%
31/1,571,316 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0357% | 2,803 |
| Middle Eastern | 0.0349% | 2,864 |
| Remaining individualsnot grpmax-eligible | 0.00499% | 20,053 |
| East Asian | 0.00446% | 22,409 |
| European (non-Finnish) | 0.000513% | 194,904 |
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.Pro84=
- Coding
- c.252T>C
- MANE Select
- NM_000311
- dbSNP
- rs62637686
- Type
- single nucleotide variant
- Location
- chr20:4699472 (GRCh38)
- Gene constraint
- LOEUF 1.036 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.18 · 70 PDB
- Residue 84
- the 'disordered' region; the '5 x 8 aa tandem repeats of p-h-g-g-g-w-g-q' region; the 'interaction with grb2, eri3 and syn1' region
Similar variants
- PRNP p.Val189Ile Uncertain significance ★★ ⚠ same condition
- PRNP c.*206A>G Benign ★★ same condition
- PRNP c.*4A>T Benign ★★ same condition
- PRNP c.*682A>G Benign ★★ same condition
- PRNP c.*697A>G Benign ★★ same condition
- PRNP c.*70G>A Benign/Likely benign ★★ same condition
- PRNP p.Ala117= Benign/Likely benign ★★ same condition
- PRNP p.Asn171Ser Benign ★★ 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/prnp-p-pro84 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown