Is PRNP p.Pro60= (c.180T>C) pathogenic?

PRNP p.Pro60= (c.180T>C) is classified Uncertain significance in PRNP (ClinVar, Single submitter, 1 submitter; last evaluated 2016-06-26). Very rare (popmax 0.00017%, nfe); Associated with spongiform encephalopathy with neuropsychiatric features.

What condition is associated with PRNP p.Pro60= (c.180T>C)?

PRNP p.Pro60= (c.180T>C) is associated with spongiform encephalopathy with neuropsychiatric features (ClinVar).

How common is PRNP p.Pro60= (c.180T>C) in the general population?

PRNP p.Pro60= (c.180T>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

PRNP p.Pro60=

c.180T>C · rs1386720703 · VCV453305

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

spongiform encephalopathy with neuropsychiatric features

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 -0.96	GERP -2.9
Overall
CADD	6.986	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,176,810 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000125% 2/1,606,144 alleles · very rare exomes 2/1,456,948 · genomes 0/149,196 · 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.Pro60=
Coding: c.180T>C
MANE Select: NM_000311
dbSNP: rs1386720703
Type: single nucleotide variant
Location: chr20:4699400 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.18 · 70 PDB
Residue 60: the 'disordered' region; the '5 x 8 aa tandem repeats of p-h-g-g-g-w-g-q' region; a UniProt-annotated variant site (sequence variant); the 'interaction with grb2, eri3 and syn1' region

Full PRNP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spongiform encephalopathy with neuropsychiatric features — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRNP p.Asp178Asn Pathogenic/Likely pathogenic ★★ ⚠ same condition
PRNP p.Glu200Lys Pathogenic ★★ ⚠ same condition
PRNP p.Pro102Leu Pathogenic ★★ same condition
PRNP p.Thr183Ala Pathogenic ★★ same condition
PRNP c.*115G>A Uncertain significance ★★ same condition
PRNP p.Met166Ile Uncertain significance ★★ ⚠ same condition
PRNP p.Met232Arg Uncertain significance ★★ ⚠ 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-pro60 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown