Is ADGRE2 p.Ser570Ter (c.1709C>A) pathogenic?

ADGRE2 p.Ser570Ter (c.1709C>A) is classified Conflicting classifications of pathogenicity in ADGRE2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-18). Rare (popmax 0.303%, eas); Associated with autosomal dominant vibratory urticaria.

What condition is associated with ADGRE2 p.Ser570Ter (c.1709C>A)?

ADGRE2 p.Ser570Ter (c.1709C>A) is associated with autosomal dominant vibratory urticaria (ClinVar).

How common is ADGRE2 p.Ser570Ter (c.1709C>A) in the general population?

ADGRE2 p.Ser570Ter (c.1709C>A) is rare (popmax 0.303%, eas) (gnomAD).

How is Vibratory urticaria inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

ADGRE2 p.Ser570Ter

c.1709C>A · rs187229047 · VCV2416266

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.303%, eas)

Conditions

autosomal dominant vibratory urticaria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 15 of 21
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.59	GERP -1.4
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.303% East Asian · 136/44,884 alleles

Filtering AF 0.261% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.246%

Overall 0.0101% 162/1,602,064 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.303%	330
Remaining individualsnot grpmax-eligible	0.0177%	5,645
South Asian	0.0167%	5,980

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.Ser570Ter
Coding: c.1709C>A
MANE Select: NM_013447
dbSNP: rs187229047
Type: single nucleotide variant
Location: chr19:14752408 (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

Disease context

autosomal dominant vibratory urticaria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Vibratory urticaria (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages

Similar variants

ADGRE2 p.Ser570= Likely benign ★ same residue
ADGRE2 p.Cys550Ter Uncertain significance ★★ same condition
ADGRE2 p.Thr277Lys Uncertain significance ★★ ⚠ same condition
ADGRE2 p.Cys85Gly Uncertain significance ★ ⚠ same condition
ADGRE2 p.Gly594Ter Conflicting classifications of pathogenicity ★ same condition
ADGRE2 p.Ile740Thr Uncertain significance ★ ⚠ same condition
ADGRE2 p.Trp195Ter Conflicting classifications of pathogenicity ★ same condition
ADGRE2 p.Trp708Ter Conflicting classifications of pathogenicity ★ same condition

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-ser570ter (accessed [today's date]).

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