Is ADGRE2 p.Asp36Val (c.107A>T) pathogenic?

ADGRE2 p.Asp36Val (c.107A>T) is classified Uncertain significance in ADGRE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-27). AlphaMissense: likely benign (0.2025); Very rare (popmax 0.0011%, sas).

How common is ADGRE2 p.Asp36Val (c.107A>T) in the general population?

ADGRE2 p.Asp36Val (c.107A>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about ADGRE2 p.Asp36Val (c.107A>T)?

AlphaMissense predicts likely benign (score 0.2025) — an in-silico prediction, not a clinical call.

ADGRE2 p.Asp36Val

c.107A>T · rs369172417 · VCV1999336

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2025 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2025	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -11.46	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.4	GERP -1.9, phastCons 0.005
Regional constraint	o/e 0.89	unconstrained · MANE · 9,655 bp · p 0.17 · regional, not allelic
Overall
CADD	13.02	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,012 alleles

Overall 6.84e-05% 1/1,461,856 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.Asp36Val
Coding: c.107A>T
MANE Select: NM_013447
dbSNP: rs369172417
Type: single nucleotide variant
Location: chr19:14774030 (GRCh38)
Gene constraint: LOEUF 1.028 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.44 · 3 PDB
Residue 36: the egf-like 1 domain; a disulfide bond

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

Similar variants

ADGRE2 p.Asp36Asn Uncertain significance ★ ⚠ same residue
ADGRE2 p.Asp36= Benign ★ 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

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-asp36val (accessed [today's date]).

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