Is PRNP p.Pro102= (c.306G>A) pathogenic?

PRNP p.Pro102= (c.306G>A) is classified Benign/Likely benign in PRNP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-01). Ultra-rare (popmax 0.09%, amr); Associated with Huntington disease-like 1.

What condition is associated with PRNP p.Pro102= (c.306G>A)?

PRNP p.Pro102= (c.306G>A) is associated with Huntington disease-like 1, inherited Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome (ClinVar).

How common is PRNP p.Pro102= (c.306G>A) in the general population?

PRNP p.Pro102= (c.306G>A) is ultra-rare (popmax 0.09%, amr) (gnomAD).

How is Huntington disease-like 1 inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

PRNP p.Pro102=

c.306G>A · rs370426100 · VCV766882

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.09%, amr)

Conditions

Huntington disease-like 1

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 0.37	GERP -1.5, phastCons 0.98
Overall
CADD	11.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.09% Admixed American · 54/60,006 alleles

Filtering AF 0.0708% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0639%

Overall 0.00539% 87/1,613,814 alleles · ultra-rare exomes 70/1,461,704 · genomes 17/152,110 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.09%	1,111
African / African-American	0.0134%	7,489
East Asian	0.00668%	14,963
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Remaining individualsnot grpmax-eligible	0.0032%	31,236
South Asian	0.0022%	45,533
European (non-Finnish)	0.00127%	78,660

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.Pro102=
Coding: c.306G>A
MANE Select: NM_000311
dbSNP: rs370426100
Type: single nucleotide variant
Location: chr20:4699526 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.18 · 70 PDB
Residue 102: the 'disordered' region; a UniProt-annotated variant site (in gsd and early-onset dementia); an α-helix; the 'interaction with grb2, eri3 and syn1' region

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

Disease context

Huntington disease-like 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: inherited Creutzfeldt-Jakob disease Gerstmann-Straussler-Scheinker syndrome kuru, susceptibility to fatal familial insomnia spongiform encephalopathy with neuropsychiatric features

For Huntington disease-like 1 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

PRNP p.Pro102Leu Pathogenic ★★ same residue
PRNP p.Pro102Ser Likely pathogenic same residue
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

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-pro102 (accessed [today's date]).

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