Is PRNP p.Gln212= (c.636G>A) pathogenic?

PRNP p.Gln212= (c.636G>A) is classified Likely benign in PRNP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-06). Ultra-rare (popmax 0.0165%, mid); Associated with kuru, susceptibility to.

What condition is associated with PRNP p.Gln212= (c.636G>A)?

PRNP p.Gln212= (c.636G>A) is associated with kuru, susceptibility to, inherited Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome (ClinVar).

How common is PRNP p.Gln212= (c.636G>A) in the general population?

PRNP p.Gln212= (c.636G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

PRNP p.Gln212=

c.636G>A · rs757784308 · VCV1576397

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

kuru, susceptibility to

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 2.6	GERP 1.5, phastCons 1
Overall
CADD	6.091	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00274% 40/1,461,894 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0096%	10,417
South Asian	0.00659%	15,176
European (non-Finnish)	0.00229%	43,703

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.Gln212=
Coding: c.636G>A
MANE Select: NM_000311
dbSNP: rs757784308
Type: single nucleotide variant
Location: chr20:4699856 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.18 · 70 PDB
Residue 212: a UniProt-annotated variant site (in gsd); the 'interaction with grb2, eri3 and syn1' region; a β-strand

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

Disease context

kuru, susceptibility to — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: inherited Creutzfeldt-Jakob disease Gerstmann-Straussler-Scheinker syndrome fatal familial insomnia Huntington disease-like 1 spongiform encephalopathy with neuropsychiatric features

Similar variants

PRNP p.Gln212Pro Conflicting classifications of pathogenicity ★ ⚠ 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
PRNP p.Gly131Val Pathogenic/Likely 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-gln212 (accessed [today's date]).

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