Is ADGRE2 p.Phe688fs (c.2063del) pathogenic?

ADGRE2 p.Phe688fs (c.2063del) is classified Uncertain significance in ADGRE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-18). Very rare (popmax 0.00134%, afr).

How common is ADGRE2 p.Phe688fs (c.2063del) in the general population?

ADGRE2 p.Phe688fs (c.2063del) is very rare (popmax 0.00134%, afr) (gnomAD).

ADGRE2 p.Phe688fs

c.2063del · rs1180038250 · VCV3022634

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

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 17 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.8	GERP -1.8
Overall
CADD	27.3	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 0.00134% African / African-American · 1/74,836 alleles

Overall 0.000658% 1/151,954 alleles · very rare

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.Phe688fs
Coding: c.2063del
MANE Select: NM_013447
dbSNP: rs1180038250
Type: Deletion
Location: chr19:14746924 (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 c.1084+19_1084+36del Benign/Likely benign ★★ same type
ADGRE2 p.Gln565fs Likely benign ★★ same type
ADGRE2 c.1085-3_1085-2del Uncertain significance ★ same type
ADGRE2 c.2353-4_2354del Uncertain significance ★ same type
ADGRE2 c.355_355+7del Uncertain significance ★ same type
ADGRE2 p.Arg675fs Uncertain significance ★ same type
ADGRE2 p.Asn69del Uncertain significance ★ same type
ADGRE2 p.Glu366del 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-phe688fs (accessed [today's date]).

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