Is VRK1 p.Pro217= (c.651C>G) pathogenic?

VRK1 p.Pro217= (c.651C>G) is classified Likely benign in VRK1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-07). Absent from gnomAD v4.1; Associated with pontocerebellar hypoplasia type 1A.

What condition is associated with VRK1 p.Pro217= (c.651C>G)?

VRK1 p.Pro217= (c.651C>G) is associated with pontocerebellar hypoplasia type 1A (ClinVar).

How common is VRK1 p.Pro217= (c.651C>G) in the general population?

VRK1 p.Pro217= (c.651C>G) is absent from gnomAD v4.1 (gnomAD).

VRK1 p.Pro217=

c.651C>G · rs2139801938 · VCV1093941

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

pontocerebellar hypoplasia type 1A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.047	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.16	GERP -0.66, phastCons 0.43
Overall
CADD	9.956	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: VRK1
Protein: p.Pro217=
Coding: c.651C>G
MANE Select: NM_003384
dbSNP: rs2139801938
Type: single nucleotide variant
Location: chr14:96855298 (GRCh38)
Gene constraint: LOEUF 0.747 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.37 · 26 PDB
Residue 217: the protein kinase domain

Full VRK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pontocerebellar hypoplasia type 1A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

VRK1 p.Pro217Leu Uncertain significance ⚠ same residue
VRK1 c.1159+1G>A Pathogenic/Likely pathogenic ★★ same condition
VRK1 c.216+1G>C Likely pathogenic ★★ same condition
VRK1 c.483+1G>A Likely pathogenic ★★ same condition
VRK1 c.889+1G>T Likely pathogenic ★★ same condition
VRK1 p.Arg321Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
VRK1 p.Arg358Ter Pathogenic ★★ same condition
VRK1 p.Arg387His Pathogenic/Likely pathogenic ★★ ⚠ 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/vrk1-p-pro217 (accessed [today's date]).

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