Is ADGRE2 p.Arg786Gln (c.2357G>A) pathogenic?

ADGRE2 p.Arg786Gln (c.2357G>A) is classified Benign in ADGRE2 (ClinVar, Single submitter, 2 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.0831); Low-frequency (popmax 2.11%, sas).

How common is ADGRE2 p.Arg786Gln (c.2357G>A) in the general population?

ADGRE2 p.Arg786Gln (c.2357G>A) is low-frequency (popmax 2.11%, sas) (gnomAD).

What do computational predictors say about ADGRE2 p.Arg786Gln (c.2357G>A)?

AlphaMissense predicts likely benign (score 0.0831) — an in-silico prediction, not a clinical call.

ADGRE2 p.Arg786Gln

c.2357G>A · rs117617387 · VCV2038299

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0831 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.11%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0831	likely benign
REVEL	0.209	benign-leaning
SaProt	LLR -8.44	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.7	GERP -0.94
Regional constraint	o/e 0.82	unconstrained · MANE · 29 kb · p 2.6e-06 · regional, not allelic
Overall
CADD	7.132	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 2.11% South Asian · 1,925/91,068 alleles

Filtering AF 2.04% ClinGen BA1/BS1 input FAF95, joint · FAF99 2%

Overall 1.64% 26,504/1,613,930 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	2.11%	47
European (non-Finnish)	1.9%	53
Remaining individualsnot grpmax-eligible	1.5%	67
Middle Eastern	0.891%	112
Ashkenazi Jewishnot grpmax-eligible	0.854%	117
Admixed American	0.648%	154
Finnishnot grpmax-eligible	0.52%	192
African / African-American	0.324%	309
East Asian	0.0111%	8,976

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: ADGRE2
Protein: p.Arg786Gln
Coding: c.2357G>A
MANE Select: NM_013447
dbSNP: rs117617387
Type: single nucleotide variant
Location: chr19:14743526 (GRCh38)
Gene constraint: LOEUF 1.028 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.44 · 3 PDB

Full ADGRE2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADGRE2 p.Arg786Trp Uncertain significance ★★ ⚠ same residue
ADGRE2 p.Ala359Gly Uncertain significance ★★ ⚠ same type
ADGRE2 p.Ala44Thr Uncertain significance ★★ ⚠ same type
ADGRE2 p.Ala554Val Uncertain significance ★★ ⚠ same type
ADGRE2 p.Ala555Ser Uncertain significance ★★ ⚠ same type
ADGRE2 p.Ala589Thr Uncertain significance ★★ ⚠ same type
ADGRE2 p.Ala603Thr Uncertain significance ★★ ⚠ same type
ADGRE2 p.Ala656Thr 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/adgre2-p-arg786gln (accessed [today's date]).

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