Is PNKD p.Pro358= (c.1074G>A) pathogenic?

PNKD p.Pro358= (c.1074G>A) is classified Likely benign in PNKD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.0406%, sas); Associated with paroxysmal nonkinesigenic dyskinesia.

What condition is associated with PNKD p.Pro358= (c.1074G>A)?

PNKD p.Pro358= (c.1074G>A) is associated with paroxysmal nonkinesigenic dyskinesia (ClinVar).

How common is PNKD p.Pro358= (c.1074G>A) in the general population?

PNKD p.Pro358= (c.1074G>A) is ultra-rare (popmax 0.0406%, sas) (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.Pro358=

c.1074G>A · rs148953301 · VCV700989

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0406%, sas)

Conditions

paroxysmal nonkinesigenic dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.4	GERP -3.8
Overall
CADD	0.093	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0406% South Asian · 37/91,064 alleles

Filtering AF 0.0303% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0267%

Overall 0.0049% 79/1,613,396 alleles · ultra-rare exomes 74/1,461,110 · genomes 5/152,286 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0406%	2,461
Middle Eastern	0.0165%	6,054
Remaining individualsnot grpmax-eligible	0.0032%	31,236
European (non-Finnish)	0.00314%	31,875
Admixed American	0.00167%	60,014
African / African-American	0.00133%	75,036

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.Pro358=
Coding: c.1074G>A
MANE Select: NM_015488
dbSNP: rs148953301
Type: single nucleotide variant
Location: chr2:218344897 (GRCh38)
Gene constraint: LOEUF 1.131 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.69

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-pro358 (accessed [today's date]).

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