Is PNKD p.Pro53= (c.159T>C) pathogenic?

PNKD p.Pro53= (c.159T>C) is classified Likely benign in PNKD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-14). Absent from gnomAD v4.1; Associated with paroxysmal nonkinesigenic dyskinesia.

What condition is associated with PNKD p.Pro53= (c.159T>C)?

PNKD p.Pro53= (c.159T>C) is associated with paroxysmal nonkinesigenic dyskinesia (ClinVar).

How common is PNKD p.Pro53= (c.159T>C) in the general population?

PNKD p.Pro53= (c.159T>C) is absent from gnomAD v4.1 (gnomAD).

How is Paroxysmal non-kinesigenic dyskinesia inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

PNKD p.Pro53=

c.159T>C · rs2469257875 · VCV2731374

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

paroxysmal nonkinesigenic dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -9	GERP -4.5
Overall
CADD	1.461	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PNKD
Protein: p.Pro53=
Coding: c.159T>C
MANE Select: NM_015488
dbSNP: rs2469257875
Type: single nucleotide variant
Location: chr2:218271472 (GRCh38)
Gene constraint: LOEUF 1.131 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.69
Residue 53: the 'disordered' region

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

Disease context

paroxysmal nonkinesigenic dyskinesia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Paroxysmal non-kinesigenic dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

PNKD c.465+3G>A Uncertain significance ★★ same condition
PNKD p.Ala167Thr Uncertain significance ★★ ⚠ same condition
PNKD p.Ala28Gly Uncertain significance ★★ ⚠ same condition
PNKD p.Ala78Val Uncertain significance ★★ ⚠ same condition
PNKD p.Arg368Gln Uncertain significance ★★ ⚠ same condition
PNKD p.Asp365Val Uncertain significance ★★ ⚠ same condition
PNKD p.Glu305Asp Uncertain significance ★★ ⚠ same condition
PNKD p.Glu48Lys Uncertain significance ★★ ⚠ 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/pnkd-p-pro53 (accessed [today's date]).

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