Is GRK2 p.Ter690= (c.2069G>A) pathogenic?

GRK2 p.Ter690= (c.2069G>A) is classified Benign in GRK2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-06). Low-frequency (popmax 2.41%, afr).

How common is GRK2 p.Ter690= (c.2069G>A) in the general population?

GRK2 p.Ter690= (c.2069G>A) is low-frequency (popmax 2.41%, afr) (gnomAD).

GRK2 p.Ter690=

c.2069G>A · rs2229537 · VCV776631

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

low-frequency (popmax 2.41%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function in a LoF-intolerant gene
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP 0.92, phastCons 1
Overall
CADD	14.3	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.41% African / African-American · 1,738/72,098 alleles

Filtering AF 2.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.28%

Overall 0.13% 2,010/1,541,254 alleles · low-frequency exomes 1,010/1,388,880 · genomes 1,000/152,374 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.41%	41
Admixed American	0.218%	459
Remaining individualsnot grpmax-eligible	0.2%	501
Middle Eastern	0.0407%	2,457
South Asian	0.00846%	11,826
European (non-Finnish)	0.00375%	26,653
East Asian	0.00229%	43,626

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: GRK2
Protein: p.Ter690=
Coding: c.2069G>A
MANE Select: NM_001619
dbSNP: rs2229537
Type: single nucleotide variant
Location: chr11:67285449 (GRCh38)
Gene constraint: LOEUF 0.29 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.36 · 20 PDB

Full GRK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GRK2 p.Tyr553= Benign ★★ same type
GRK2 c.503+1G>A Uncertain significance ★ same type
GRK2 p.Arg435Gln Uncertain significance ★ ⚠ same type
GRK2 p.Asp481Asn Uncertain significance ★ ⚠ same type
GRK2 p.Asp527Asn Uncertain significance ★ ⚠ same type
GRK2 p.Ser121Leu Uncertain significance ★ ⚠ same type
GRK2 p.Thr528Ile Uncertain significance ★ ⚠ same type
GRK2 p.Val246Phe 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/grk2-p-ter690 (accessed [today's date]).

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