Is PRKN p.Gly319= (c.957T>C) pathogenic?

PRKN p.Gly319= (c.957T>C) is classified Benign/Likely benign in PRKN (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-16). Low-frequency (popmax 3.4%, afr); Associated with autosomal recessive juvenile Parkinson disease 2.

What condition is associated with PRKN p.Gly319= (c.957T>C)?

PRKN p.Gly319= (c.957T>C) is associated with autosomal recessive juvenile Parkinson disease 2 (ClinVar).

How common is PRKN p.Gly319= (c.957T>C) in the general population?

PRKN p.Gly319= (c.957T>C) is low-frequency (popmax 3.4%, afr) (gnomAD).

How is Young-onset Parkinson disease inherited?

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

PRKN p.Gly319=

c.957T>C · rs144340740 · VCV415532

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.4%, afr)

Conditions

autosomal recessive juvenile Parkinson disease 2

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 -11	GERP -5.4
Overall
CADD	0.014	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.4% African / African-American · 2,554/75,038 alleles

Filtering AF 3.29% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.25%

Overall 0.178% 2,868/1,614,188 alleles · low-frequency exomes 1,411/1,461,884 · genomes 1,457/152,304 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.4%	29
Admixed American	0.207%	484
Remaining individualsnot grpmax-eligible	0.203%	492
Middle Eastern	0.165%	606
South Asian	0.0154%	6,506
European (non-Finnish)	0.00322%	31,053
East Asian	0.00223%	44,880

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: PRKN
Protein: p.Gly319=
Coding: c.957T>C
MANE Select: NM_004562
dbSNP: rs144340740
Type: single nucleotide variant
Location: chr6:161548980 (GRCh38)
Gene constraint: LOEUF 1.17 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 79.10 · 21 PDB
Residue 319: an α-helix; the 'triad supradomain' region

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

Disease context

autosomal recessive juvenile Parkinson disease 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Young-onset Parkinson disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

PRKN p.Arg275Trp Pathogenic/Likely pathogenic ★★ same condition
PRKN p.Arg33Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
PRKN p.Arg42Pro Pathogenic ★★ same condition
PRKN p.Cys212Tyr Pathogenic ★★ same condition
PRKN p.Cys253Tyr Pathogenic/Likely pathogenic ★★ same condition
PRKN p.Cys441Arg Pathogenic/Likely pathogenic ★★ same condition
PRKN p.Gln25Ter Pathogenic/Likely pathogenic ★★ same condition
PRKN p.Gly284Arg 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/prkn-p-gly319 (accessed [today's date]).

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