Is PRKRA p.Ser290= (c.870C>T) pathogenic?

PRKRA p.Ser290= (c.870C>T) is classified Uncertain significance in PRKRA (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Ultra-rare (popmax 0.067%, sas); Associated with dystonia 16.

What condition is associated with PRKRA p.Ser290= (c.870C>T)?

PRKRA p.Ser290= (c.870C>T) is associated with dystonia 16 (ClinVar).

How common is PRKRA p.Ser290= (c.870C>T) in the general population?

PRKRA p.Ser290= (c.870C>T) is ultra-rare (popmax 0.067%, sas) (gnomAD).

How is Dystonia 16 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

PRKRA p.Ser290=

c.870C>T · rs537898766 · VCV332621

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.067%, sas)

Conditions

dystonia 16

⚠ 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 1.8	GERP 1, phastCons 1
Overall
CADD	10.37	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.067% South Asian · 61/91,080 alleles

Filtering AF 0.0535% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0486%

Overall 0.00378% 61/1,614,230 alleles · ultra-rare exomes 57/1,461,874 · genomes 4/152,356 · joint denominator

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: PRKRA
Protein: p.Ser290=
Coding: c.870C>T
MANE Select: NM_003690
dbSNP: rs537898766
Type: single nucleotide variant
Location: chr2:178432169 (GRCh38)

Full PRKRA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dystonia 16 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Dystonia 16 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

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/prkra-p-ser290 (accessed [today's date]).

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