Is PRNP p.Asp202= (c.606C>T) pathogenic?

PRNP p.Asp202= (c.606C>T) is classified Conflicting classifications of pathogenicity in PRNP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-07-01). Ultra-rare (popmax 0.0186%, nfe); Associated with Huntington disease-like 1.

What condition is associated with PRNP p.Asp202= (c.606C>T)?

PRNP p.Asp202= (c.606C>T) is associated with Huntington disease-like 1 (ClinVar).

How common is PRNP p.Asp202= (c.606C>T) in the general population?

PRNP p.Asp202= (c.606C>T) is ultra-rare (popmax 0.0186%, nfe) (gnomAD).

How is Huntington disease-like 1 inherited?

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

PRNP p.Asp202=

c.606C>T · rs371948269 · VCV871373

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0186%, nfe)

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 -1.4	GERP -2.6
Overall
CADD	8.066	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0186% European (non-Finnish) · 220/1,180,008 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0158%

Overall 0.0142% 229/1,613,786 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0186%	5,364
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,867
Remaining individualsnot grpmax-eligible	0.0064%	15,621
Admixed American	0.00167%	59,964
Finnishnot grpmax-eligible	0.00156%	64,006

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.Asp202=
Coding: c.606C>T
MANE Select: NM_000311
dbSNP: rs371948269
Type: single nucleotide variant
Location: chr20:4699826 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.18 · 70 PDB
Residue 202: a disulfide bond; 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

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

For Huntington disease-like 1 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

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-asp202 (accessed [today's date]).

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