Is ADGRE2 p.Thr108= (c.324A>T) pathogenic?

ADGRE2 p.Thr108= (c.324A>T) is classified Likely benign in ADGRE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-30). Ultra-rare (popmax 0.067%, sas).

How common is ADGRE2 p.Thr108= (c.324A>T) in the general population?

ADGRE2 p.Thr108= (c.324A>T) is ultra-rare (popmax 0.067%, sas) (gnomAD).

ADGRE2 p.Thr108=

c.324A>T · rs778934730 · VCV1930564

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.067%, sas)

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 -20	GERP -3.1
Overall
CADD	0.023	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.067% South Asian · 61/91,086 alleles

Filtering AF 0.0535% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0486%

Overall 0.00434% 70/1,614,022 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.067%	1,493
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.000678%	147,503

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.Thr108=
Coding: c.324A>T
MANE Select: NM_013447
dbSNP: rs778934730
Type: single nucleotide variant
Location: chr19:14772373 (GRCh38)
Gene constraint: LOEUF 1.028 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.44 · 3 PDB
Residue 108: the egf-like 2; calcium-binding domain; a disulfide bond

Full ADGRE2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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
ADGRE2 p.Ala664Gly 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-thr108 (accessed [today's date]).

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