Is PRNP p.Gly53= (c.159C>T) pathogenic?

PRNP p.Gly53= (c.159C>T) is classified Benign/Likely benign in PRNP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-05-09). Ultra-rare (popmax 0.0672%, mid); Associated with Gerstmann-Straussler-Scheinker syndrome.

What condition is associated with PRNP p.Gly53= (c.159C>T)?

PRNP p.Gly53= (c.159C>T) is associated with Gerstmann-Straussler-Scheinker syndrome, inherited Creutzfeldt-Jakob disease, kuru, susceptibility to (ClinVar).

How common is PRNP p.Gly53= (c.159C>T) in the general population?

PRNP p.Gly53= (c.159C>T) is ultra-rare (popmax 0.0672%, mid) (gnomAD).

How is Gerstmann-Straussler-Scheinker syndrome inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

PRNP p.Gly53=

c.159C>T · rs776188950 · VCV338645

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0672%, mid)

Conditions

Gerstmann-Straussler-Scheinker syndrome

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 -2.6
Overall
CADD	2.372	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0672% Middle Eastern · 4/5,952 alleles

Filtering AF 0.0229% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0163%

Overall 0.00508% 82/1,613,174 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0672%	1,488
South Asian	0.0275%	3,639
East Asian	0.00669%	14,944
Remaining individualsnot grpmax-eligible	0.0048%	20,824
European (non-Finnish)	0.00398%	25,103

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.Gly53=
Coding: c.159C>T
MANE Select: NM_000311
dbSNP: rs776188950
Type: single nucleotide variant
Location: chr20:4699379 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.18 · 70 PDB
Residue 53: 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

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

Disease context

Gerstmann-Straussler-Scheinker syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: inherited Creutzfeldt-Jakob disease kuru, susceptibility to fatal familial insomnia Huntington disease-like 1 spongiform encephalopathy with neuropsychiatric features

For Gerstmann-Straussler-Scheinker syndrome (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adult

Similar variants

PRNP p.Ala117Val Pathogenic ★★ ⚠ same condition
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

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-gly53 (accessed [today's date]).

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