Is PRKRA p.Pro280= (c.840C>T) pathogenic?

PRKRA p.Pro280= (c.840C>T) is classified Likely benign in PRKRA (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-28). Very rare (popmax 0.00668%, eas); Associated with dystonia 16.

What condition is associated with PRKRA p.Pro280= (c.840C>T)?

PRKRA p.Pro280= (c.840C>T) is associated with dystonia 16 (ClinVar).

How common is PRKRA p.Pro280= (c.840C>T) in the general population?

PRKRA p.Pro280= (c.840C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

How is Dystonia 16 inherited?

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

PRKRA p.Pro280=

c.840C>T · rs1176724773 · VCV1554500

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Conditions

dystonia 16

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 -1.2	GERP -3.8
Overall
CADD	7.381	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,886 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000619% 10/1,614,230 alleles · very rare exomes 10/1,461,866 · genomes 0/152,364 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,962
European (non-Finnish)	0.000593%	168,577

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.Pro280=
Coding: c.840C>T
MANE Select: NM_003690
dbSNP: rs1176724773
Type: single nucleotide variant
Location: chr2:178432199 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.55 · 2 PDB
Residue 280: the drbm 3 domain; a β-strand; the 'sufficient for self-association and interaction with tarbp2' region

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

Similar variants

PRKRA c.-104G>A Uncertain significance ★★ same condition
PRKRA c.-117C>T Uncertain significance ★★ same condition
PRKRA c.-124C>A Uncertain significance ★★ same condition
PRKRA c.-125G>A Uncertain significance ★★ same condition
PRKRA c.-133C>G Uncertain significance ★★ same condition
PRKRA c.-149T>C Uncertain significance ★★ same condition
PRKRA c.-64C>G Uncertain significance ★★ same condition
PRKRA p.Ala29Thr 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/prkra-p-pro280 (accessed [today's date]).

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