Is PNKD p.Pro306= (c.918C>T) pathogenic?

PNKD p.Pro306= (c.918C>T) is classified Likely benign in PNKD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-07). Very rare (popmax 0.00268%, afr); Associated with paroxysmal nonkinesigenic dyskinesia.

What condition is associated with PNKD p.Pro306= (c.918C>T)?

PNKD p.Pro306= (c.918C>T) is associated with paroxysmal nonkinesigenic dyskinesia (ClinVar).

How common is PNKD p.Pro306= (c.918C>T) in the general population?

PNKD p.Pro306= (c.918C>T) is very rare (popmax 0.00268%, afr) (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.Pro306=

c.918C>T · rs780334841 · VCV1648190

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00268%, afr)

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 -20	GERP -3.5
Overall
CADD	0.22	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00268% African / African-American · 2/74,546 alleles

Filtering AF 0.000445% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000167%

Overall 0.000503% 8/1,591,808 alleles · very rare exomes 7/1,439,682 · genomes 1/152,126 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00268%	37,273
Admixed American	0.00178%	56,320
Remaining individualsnot grpmax-eligible	0.00162%	61,664
South Asian	0.00114%	87,736
European (non-Finnish)	0.000257%	389,698

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.Pro306=
Coding: c.918C>T
MANE Select: NM_015488
dbSNP: rs780334841
Type: single nucleotide variant
Location: chr2:218344504 (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-pro306 (accessed [today's date]).

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