ADGRG7

Chr 3

adhesion G protein-coupled receptor G7

Also known as: GPR128

NCBI Gene: 84873 ENSG00000144820 UniProt: Q96K78 OMIM: 612307

Predicted to enable G protein-coupled receptor activity. Predicted to be involved in adenylate cyclase-activating G protein-coupled receptor signaling pathway. Predicted to be located in membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.12

Clinical Summary— ADGRG7

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

117 VUS of 142 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.12LOEUF

pLI 0.000

Z-score 0.96

OE 0.83 (0.62–1.12)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.38Z-score

OE missense 0.95 (0.87–1.03)

401 obs / 422.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.83 (0.62–1.12)

0≤0.351.4

Missense OE?0.95 (0.87–1.03)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 30 / 36.3Missense obs/exp: 401 / 422.8Syn Z: -0.83

This gene — mechanism propensity

0.82top 10%

GOF

0.72top 25%

LOF

0.2189th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

142 submitted variants in ClinVar

ClinVar

Classification Summary

VUS117

Likely Benign13

Benign3

Conflicting2

117

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	116	0	0	117
Likely Benign	0	11	1	1	13
Benign	0	1	0	2	3
Conflicting	—				2
Total	1	128	1	3	135

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

9 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap ADGRG7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →