Is GRK6 p.Pro573= (c.1719C>T) pathogenic?

GRK6 p.Pro573= (c.1719C>T) is classified Uncertain significance in GRK6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-10). Very rare (popmax 8.48e-05%, nfe).

How common is GRK6 p.Pro573= (c.1719C>T) in the general population?

GRK6 p.Pro573= (c.1719C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

GRK6 p.Pro573=

c.1719C>T · rs2481127818 · VCV3102621

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.036	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -0.25, phastCons 1
Overall
CADD	11.33	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,178,772 alleles

Overall 6.85e-05% 1/1,459,648 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: GRK6
Protein: p.Pro573=
Coding: c.1719C>T
MANE Select: NM_001004106
dbSNP: rs2481127818
Type: single nucleotide variant
Location: chr5:177441778 (GRCh38)
Gene constraint: LOEUF 0.604 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.22 · 3 PDB

Full GRK6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GRK6 c.*33G>A Uncertain significance ★ same type
GRK6 p.Ala258Val Uncertain significance ★ ⚠ same type
GRK6 p.Ala429Val Uncertain significance ★ ⚠ same type
GRK6 p.Arg123Gln Uncertain significance ★ ⚠ same type
GRK6 p.Arg123Leu Uncertain significance ★ ⚠ same type
GRK6 p.Arg123Trp Uncertain significance ★ ⚠ same type
GRK6 p.Arg169Cys Uncertain significance ★ ⚠ same type
GRK6 p.Arg23Cys Uncertain significance ★ ⚠ same type

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/grk6-p-pro573 (accessed [today's date]).

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