Is VRK1 p.Pro206= (c.618A>G) pathogenic?

VRK1 p.Pro206= (c.618A>G) is classified Likely benign in VRK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-15). Very rare (popmax 0.00167%, amr); Associated with pontocerebellar hypoplasia type 1A.

What condition is associated with VRK1 p.Pro206= (c.618A>G)?

VRK1 p.Pro206= (c.618A>G) is associated with pontocerebellar hypoplasia type 1A (ClinVar).

How common is VRK1 p.Pro206= (c.618A>G) in the general population?

VRK1 p.Pro206= (c.618A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

VRK1 p.Pro206=

c.618A>G · rs773555796 · VCV1160241

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

pontocerebellar hypoplasia type 1A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.078	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.39	GERP -3.9
Overall
CADD	7.895	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,022 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000274% 4/1,461,814 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,022
European (non-Finnish)	0.000254%	393,324

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: VRK1
Protein: p.Pro206=
Coding: c.618A>G
MANE Select: NM_003384
dbSNP: rs773555796
Type: single nucleotide variant
Location: chr14:96855265 (GRCh38)
Gene constraint: LOEUF 0.747 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.37 · 26 PDB
Residue 206: the protein kinase domain; an α-helix

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.Pro206Gln Uncertain significance ★ ⚠ same residue
VRK1 p.Pro206Ser Uncertain significance ★ ⚠ same residue
VRK1 p.Pro206Ala 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

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-pro206 (accessed [today's date]).

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