Is ADGRG2 p.Arg900Gln (c.2699G>A) pathogenic?

ADGRG2 p.Arg900Gln (c.2699G>A) is classified Likely benign in ADGRG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-01). AlphaMissense: likely benign (0.2937); Ultra-rare (popmax 0.0279%, nfe).

How common is ADGRG2 p.Arg900Gln (c.2699G>A) in the general population?

ADGRG2 p.Arg900Gln (c.2699G>A) is ultra-rare (popmax 0.0279%, nfe) (gnomAD).

What do computational predictors say about ADGRG2 p.Arg900Gln (c.2699G>A)?

AlphaMissense predicts likely benign (score 0.2937) — an in-silico prediction, not a clinical call.

ADGRG2 p.Arg900Gln

c.2699G>A · rs139650895 · VCV2660118

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2937 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0279%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2937	likely benign
REVEL	0.274	benign-leaning
SaProt	LLR -10.36	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 2.9, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 5,265 bp · p 0.88 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0279% European (non-Finnish) · 235/840,925 alleles

Filtering AF 0.025% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0239%

Overall 0.0214% 246/1,148,348 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0279%	3,578
African / African-American	0.00896%	11,160
Admixed American	0.00665%	15,042
Remaining individualsnot grpmax-eligible	0.00439%	22,784
South Asian	0.00183%	54,789

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.Arg900Gln
Coding: c.2699G>A
MANE Select: NM_001079858
dbSNP: rs139650895
Type: single nucleotide variant
Location: chrX:18996068 (GRCh38)
Structure: AlphaFold pLDDT 62.76
Residue 900: a UniProt-annotated variant site (in cbavdx; the protein is undetectable); a UniProt-annotated variant site (in cbavdx; uncertain significance); a UniProt-annotated variant site (in cbavdx; likely pathogenic)

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

Similar variants

ADGRG2 p.Arg900Trp Uncertain significance ★ same residue
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

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-arg900gln (accessed [today's date]).

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