Is PRNP p.Leu19= (c.57G>A) pathogenic?

PRNP p.Leu19= (c.57G>A) is classified Likely benign in PRNP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-18). Very rare (popmax 0.00167%, amr); Associated with Huntington disease-like 1.

What condition is associated with PRNP p.Leu19= (c.57G>A)?

PRNP p.Leu19= (c.57G>A) is associated with Huntington disease-like 1 (ClinVar).

How common is PRNP p.Leu19= (c.57G>A) in the general population?

PRNP p.Leu19= (c.57G>A) is very rare (popmax 0.00167%, 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.Leu19=

c.57G>A · rs1490413413 · VCV1606105

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, 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 -0.56	GERP -2.9, phastCons 0.001
Overall
CADD	4.414	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,028 alleles

Overall 6.84e-05% 1/1,461,760 alleles · very rare

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.Leu19=
Coding: c.57G>A
MANE Select: NM_000311
dbSNP: rs1490413413
Type: single nucleotide variant
Location: chr20:4699277 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.18 · 70 PDB

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-leu19 (accessed [today's date]).

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