Is ADGRE2 p.Gln565fs (c.1693_1709del) pathogenic?

ADGRE2 p.Gln565fs (c.16931709del) is classified Likely benign in ADGRE2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). Rare (popmax 0.763%, sas); Associated with autosomal dominant vibratory urticaria.

What condition is associated with ADGRE2 p.Gln565fs (c.1693_1709del)?

ADGRE2 p.Gln565fs (c.1693_1709del) is associated with autosomal dominant vibratory urticaria, vibratory urticaria (ClinVar).

How common is ADGRE2 p.Gln565fs (c.1693_1709del) in the general population?

ADGRE2 p.Gln565fs (c.1693_1709del) is rare (popmax 0.763%, sas) (gnomAD).

How is Vibratory urticaria inherited?

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

ADGRE2 p.Gln565fs

c.1693_1709del · rs375427337 · VCV708623

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.763%, sas)

Conditions

autosomal dominant vibratory urticaria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 15 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -20	GERP -3.4
Overall
CADD	34.0	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 0.763% South Asian · 695/91,060 alleles

Filtering AF 0.716% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.697%

Overall 0.374% 6,030/1,613,850 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.763%	131
Middle Eastern	0.627%	160
European (non-Finnish)	0.401%	249
Ashkenazi Jewishnot grpmax-eligible	0.378%	264
Remaining individualsnot grpmax-eligible	0.328%	305
Finnishnot grpmax-eligible	0.236%	424
African / African-American	0.0707%	1,414
Admixed American	0.0667%	1,499
East Asian	0.00223%	44,864

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.Gln565fs
Coding: c.1693_1709del
MANE Select: NM_013447
dbSNP: rs375427337
Type: Deletion
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

Also linked: vibratory urticaria

For Vibratory urticaria (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages

Similar variants

ADGRE2 p.Gln565Lys Uncertain significance ★★ ⚠ same residue
ADGRE2 p.Gln565Arg Uncertain significance ★ ⚠ same residue
ADGRE2 p.Cys550Ter Uncertain significance ★★ same condition
ADGRE2 p.Thr277Lys Uncertain significance ★★ ⚠ same condition
ADGRE2 p.Ala307Val Benign/Likely benign ★★ ⚠ same condition
ADGRE2 p.Asn640Ser Benign/Likely benign ★★ same condition
ADGRE2 p.Leu614Phe Benign ★★ same condition
ADGRE2 p.Gln426Ter Likely pathogenic ★ 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-gln565fs (accessed [today's date]).

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