Is ADGRE3 p.Val184Ile (c.550G>A) pathogenic?

ADGRE3 p.Val184Ile (c.550G>A) is classified Likely benign in ADGRE3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-30). AlphaMissense: likely benign (0.0728); Very rare (popmax 0.00133%, afr).

How common is ADGRE3 p.Val184Ile (c.550G>A) in the general population?

ADGRE3 p.Val184Ile (c.550G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ADGRE3 p.Val184Ile (c.550G>A)?

AlphaMissense predicts likely benign (score 0.0728) — an in-silico prediction, not a clinical call.

ADGRE3 p.Val184Ile

c.550G>A · VCV3497433

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0728 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0728	likely benign
REVEL	0.009	strongly benign-leaning
SaProt	LLR -6.24	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -2.8
Regional constraint	o/e 0.92	unconstrained · MANE · 55 kb · p 0.027 · regional, not allelic
Overall
CADD	0.044	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 0.00133% African / African-American · 1/74,992 alleles

Overall 6.84e-05% 1/1,461,728 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: ADGRE3
Protein: p.Val184Ile
Coding: c.550G>A
MANE Select: NM_032571
Type: single nucleotide variant
Location: chr19:14655009 (GRCh38)
Gene constraint: LOEUF 1.265 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.74
Residue 184: the gain-b domain

Full ADGRE3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADGRE3 p.Ala198Glu Uncertain significance ★ ⚠ same type
ADGRE3 p.Ala198Ser Uncertain significance ★ ⚠ same type
ADGRE3 p.Ala342Thr Uncertain significance ★ ⚠ same type
ADGRE3 p.Ala374Val Uncertain significance ★ ⚠ same type
ADGRE3 p.Asn39Ser Uncertain significance ★ ⚠ same type
ADGRE3 p.Asn450Asp Uncertain significance ★ ⚠ same type
ADGRE3 p.Asn538Ser Uncertain significance ★ ⚠ same type
ADGRE3 p.Asn66Asp 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/adgre3-p-val184ile (accessed [today's date]).

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