Is PNKD p.Arg94= (c.280C>A) pathogenic?

PNKD p.Arg94= (c.280C>A) is classified Likely benign in PNKD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-14). Very rare (popmax 0.000593%, nfe); Associated with paroxysmal nonkinesigenic dyskinesia.

What condition is associated with PNKD p.Arg94= (c.280C>A)?

PNKD p.Arg94= (c.280C>A) is associated with paroxysmal nonkinesigenic dyskinesia (ClinVar).

How common is PNKD p.Arg94= (c.280C>A) in the general population?

PNKD p.Arg94= (c.280C>A) is very rare (popmax 0.000593%, nfe) (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.Arg94=

c.280C>A · rs754138242 · VCV1443211

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Conditions

paroxysmal nonkinesigenic dyskinesia

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4	GERP 1.4, phastCons 1
Overall
CADD	13.65	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000593% European (non-Finnish) · 7/1,179,896 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000496% 8/1,613,824 alleles · very rare exomes 8/1,461,748 · genomes 0/152,076 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,500
European (non-Finnish)grpmax	0.000593%	168,556

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PNKD
Protein: p.Arg94=
Coding: c.280C>A
MANE Select: NM_015488
dbSNP: rs754138242
Type: single nucleotide variant
Location: chr2:218339826 (GRCh38)

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)

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-arg94 (accessed [today's date]).

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