Is VRK1 p.Pro79= (c.237T>G) pathogenic?

VRK1 p.Pro79= (c.237T>G) is classified Likely benign in VRK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-09). Very rare (popmax 0.0022%, sas); Associated with pontocerebellar hypoplasia type 1A.

What condition is associated with VRK1 p.Pro79= (c.237T>G)?

VRK1 p.Pro79= (c.237T>G) is associated with pontocerebellar hypoplasia type 1A (ClinVar).

How common is VRK1 p.Pro79= (c.237T>G) in the general population?

VRK1 p.Pro79= (c.237T>G) is very rare (popmax 0.0022%, sas) (gnomAD).

VRK1 p.Pro79=

c.237T>G · rs768944518 · VCV2764268

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

pontocerebellar hypoplasia type 1A

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 0.68	GERP -0.67, phastCons 1
Overall
CADD	10.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,074 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000137% 2/1,461,118 alleles · very rare

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.Pro79=
Coding: c.237T>G
MANE Select: NM_003384
dbSNP: rs768944518
Type: single nucleotide variant
Location: chr14:96846115 (GRCh38)
Gene constraint: LOEUF 0.747 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.37 · 26 PDB
Residue 79: 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.Pro79Leu 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-pro79 (accessed [today's date]).

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