Is ADGRE2 p.Glu720Asp (c.2160A>C) pathogenic?

ADGRE2 p.Glu720Asp (c.2160A>C) is classified Benign in ADGRE2 (ClinVar, Single submitter, 2 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0902); Common (popmax 24.4%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about ADGRE2 p.Glu720Asp (c.2160A>C)?

AlphaMissense predicts likely benign (score 0.0902) — an in-silico prediction, not a clinical call.

ADGRE2 p.Glu720Asp

Q: How common is ADGRE2 p.Glu720Asp (c.2160A>C) in the general population?

ADGRE2 p.Glu720Asp (c.2160A>C) is common (popmax 24.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2160A>C · rs57865820 · VCV2126075

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0902 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 24.4%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0902	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -7.05	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 -20	GERP -3.4
Regional constraint	o/e 0.82	unconstrained · MANE · 29 kb · p 2.6e-06 · regional, not allelic
Overall
CADD	0.038	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 24.4% African / African-American · 18,197/74,442 alleles

Filtering AF 24.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 24%

Overall 1.27% 20,427/1,606,770 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	24.4%	4
Remaining individualsnot grpmax-eligible	1.53%	65
Admixed American	1.48%	67
Middle Eastern	0.545%	183
Ashkenazi Jewishnot grpmax-eligible	0.0778%	1,285
South Asian	0.0341%	2,934
European (non-Finnish)	0.0255%	3,926

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.Glu720Asp
Coding: c.2160A>C
MANE Select: NM_013447
dbSNP: rs57865820
Type: single nucleotide variant
Location: chr19:14746255 (GRCh38)
Gene constraint: LOEUF 1.028 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.44 · 3 PDB
Residue 720: a UniProt-annotated variant site (in)

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

Similar variants

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
ADGRE2 p.Ala664Gly 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-glu720asp (accessed [today's date]).

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