Is ADGRE2 p.Phe586fs (c.1755_1756del) pathogenic?

ADGRE2 p.Phe586fs (c.17551756del) is classified Benign in ADGRE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-28). Low-frequency (popmax 1.1%, sas).

How common is ADGRE2 p.Phe586fs (c.1755_1756del) in the general population?

ADGRE2 p.Phe586fs (c.1755_1756del) is low-frequency (popmax 1.1%, sas) (gnomAD).

ADGRE2 p.Phe586fs

c.1755_1756del · rs534018804 · VCV730627

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

low-frequency (popmax 1.1%, sas)

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 10	GERP 1.7, phastCons 1
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	GA-rich low complexity · ambiguous alignment · confidence, not pathogenicity

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.1% South Asian · 1,004/91,078 alleles

Filtering AF 1.05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.02%

Overall 0.0655% 1,058/1,614,112 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.1%	91
Remaining individualsnot grpmax-eligible	0.0784%	1,276
Middle Eastern	0.033%	3,030
East Asian	0.00223%	44,882
European (non-Finnish)	0.000169%	590,005

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.Phe586fs
Coding: c.1755_1756del
MANE Select: NM_013447
dbSNP: rs534018804
Type: Microsatellite
Location: chr19:14752361 (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.5VFL[1] Uncertain significance ★ same type
ADGRE2 p.Leu10_Ala11insValPheLeu Uncertain significance ★ same type
ADGRE2 p.Trp708fs Uncertain significance ★ same type
ADGRE2 c.1416+12_1416+14del Likely benign ★ same type
ADGRE2 c.1591-16_1591-14del Likely benign ★ same type
ADGRE2 c.2092-17_2092-15del Likely benign ★ same type
ADGRE2 c.2464-17AT[5] Likely benign ★ same type
ADGRE2 c.2464-17AT[7] Likely benign ★ 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-phe586fs (accessed [today's date]).

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