Is ADGRE2 p.Pro19= (c.57G>T) pathogenic?

ADGRE2 p.Pro19= (c.57G>T) is classified Likely benign in ADGRE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-21). Ultra-rare (popmax 0.0183%, mid).

How common is ADGRE2 p.Pro19= (c.57G>T) in the general population?

ADGRE2 p.Pro19= (c.57G>T) is ultra-rare (popmax 0.0183%, mid) (gnomAD).

ADGRE2 p.Pro19=

c.57G>T · VCV3683757

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.7	GERP -2.8
Overall
CADD	0.415	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0183% Middle Eastern · 1/5,472 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000279% 4/1,433,660 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0183%	5,472
Remaining individualsnot grpmax-eligible	0.00163%	61,260
European (non-Finnish)	0.000172%	581,318

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.Pro19=
Coding: c.57G>T
MANE Select: NM_013447
Type: single nucleotide variant
Location: chr19:14774281 (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.Pro19Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-pro19 (accessed [today's date]).

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