Is PNKD p.Ser274= (c.822A>G) pathogenic?

PNKD p.Ser274= (c.822A>G) is classified Likely benign in PNKD (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-08). Absent from gnomAD v4.1; Associated with paroxysmal nonkinesigenic dyskinesia.

What condition is associated with PNKD p.Ser274= (c.822A>G)?

PNKD p.Ser274= (c.822A>G) is associated with paroxysmal nonkinesigenic dyskinesia (ClinVar).

How common is PNKD p.Ser274= (c.822A>G) in the general population?

PNKD p.Ser274= (c.822A>G) 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.Ser274=

c.822A>G · rs2106297256 · VCV1082111

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

⚠ 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 -4.4	GERP -3.6
Overall
CADD	5.766	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.Ser274=
Coding: c.822A>G
MANE Select: NM_015488
dbSNP: rs2106297256
Type: single nucleotide variant
Location: chr2:218343540 (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-ser274 (accessed [today's date]).

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