Is PNKD p.Pro341Ser (c.1021C>T) pathogenic?

PNKD p.Pro341Ser (c.1021C>T) is classified Uncertain significance in PNKD (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-03). AlphaMissense: likely pathogenic (0.9761); Absent from gnomAD v4.1; Associated with paroxysmal nonkinesigenic dyskinesia.

What condition is associated with PNKD p.Pro341Ser (c.1021C>T)?

PNKD p.Pro341Ser (c.1021C>T) is associated with paroxysmal nonkinesigenic dyskinesia (ClinVar).

How common is PNKD p.Pro341Ser (c.1021C>T) in the general population?

PNKD p.Pro341Ser (c.1021C>T) 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.

What do computational predictors say about PNKD p.Pro341Ser (c.1021C>T)?

AlphaMissense predicts likely pathogenic (score 0.9761) — an in-silico prediction, not a clinical call.

PNKD p.Pro341Ser

c.1021C>T · VCV4797250

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9761 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

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
AlphaMissense	0.9761	likely pathogenic
REVEL	0.963	strongly pathogenic-leaning
SaProt	LLR -13.05	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 74 kb · p 0.84 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Pro341Ser
Coding: c.1021C>T
MANE Select: NM_015488
Type: single nucleotide variant
Location: chr2:218344844 (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-pro341ser (accessed [today's date]).

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