Is ADGRG2 p.Pro774= (c.2322G>A) pathogenic?

ADGRG2 p.Pro774= (c.2322G>A) is classified Likely benign in ADGRG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-18). Very rare (popmax 0.000944%, nfe).

How common is ADGRG2 p.Pro774= (c.2322G>A) in the general population?

ADGRG2 p.Pro774= (c.2322G>A) is very rare (popmax 0.000944%, nfe) (gnomAD).

ADGRG2 p.Pro774=

c.2322G>A · VCV4949172

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000944%, nfe)

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 -1.9	GERP -5.8
Overall
CADD	0.566	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000944% European (non-Finnish) · 8/847,679 alleles

Filtering AF 0.000406% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000293%

Overall 0.000691% 8/1,157,339 alleles · very rare exomes 7/1,045,789 · genomes 1/111,550 · joint denominator

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: ADGRG2
Protein: p.Pro774=
Coding: c.2322G>A
MANE Select: NM_001079858
Type: single nucleotide variant
Location: chrX:18999869 (GRCh38)
Structure: AlphaFold pLDDT 62.76
Residue 774: a UniProt-annotated variant site (in cbavdx; the protein is undetectable); a UniProt-annotated variant site (in cbavdx; uncertain significance)

Full ADGRG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADGRG2 c.710+4T>C Benign ★★ same type
ADGRG2 p.Asn771Ser Benign ★★ same type
ADGRG2 p.His290Gln Benign ★★ same type
ADGRG2 p.Arg825Ter Pathogenic ★ same type
ADGRG2 p.Ser84Ter Pathogenic ★ same type
ADGRG2 c.119-4A>G Uncertain significance ★ same type
ADGRG2 p.Ala670Thr Uncertain significance ★ ⚠ same type
ADGRG2 p.Ala686Thr 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/adgrg2-p-pro774 (accessed [today's date]).

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