PRNP p.Pro76=
c.228C>T · rs112637437 · VCV218578
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0718%, sas)
Conditions
2
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 -6.6 | GERP -1.5 |
| Overall | ||
| CADD | 0.627 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0718%
South Asian · 65/90,486 alleles
Filtering AF
0.0578%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0527%
Overall
0.0122%
196/1,608,980 alleles · ultra-rare
exomes 187/1,458,720 · genomes 9/150,260 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0718% | 1,392 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0272% | 3,673 |
| African / African-American | 0.0108% | 9,285 |
| European (non-Finnish) | 0.00926% | 10,804 |
| Remaining individualsnot grpmax-eligible | 0.00803% | 12,449 |
| Finnishnot grpmax-eligible | 0.00157% | 63,700 |
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.Pro76=
- Coding
- c.228C>T
- MANE Select
- NM_000311
- dbSNP
- rs112637437
- Type
- single nucleotide variant
- Location
- chr20:4699448 (GRCh38)
- Gene constraint
- LOEUF 1.036 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.18 · 70 PDB
- Residue 76
- the 'disordered' region; the '5 x 8 aa tandem repeats of p-h-g-g-g-w-g-q' region; a turn; the 'interaction with grb2, eri3 and syn1' region
Similar variants
- PRNP p.Arg148His Likely pathogenic ★★ ⚠ same condition
- PRNP p.Arg208His Pathogenic/Likely pathogenic ★★ ⚠ same condition
- PRNP p.Asp178Asn Pathogenic/Likely pathogenic ★★ ⚠ same condition
- PRNP p.Gln217Arg Likely pathogenic ★★ ⚠ same condition
- PRNP p.Glu200Lys Pathogenic ★★ ⚠ same condition
- PRNP p.Gly131Val Pathogenic/Likely pathogenic ★★ same condition
- PRNP p.Phe198Ser Pathogenic ★★ ⚠ same condition
- PRNP p.Pro102Leu Pathogenic ★★ 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-pro76 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown