Is ADGRE2 p.Cys147Phe (c.440G>T) pathogenic?

ADGRE2 p.Cys147Phe (c.440G>T) is classified Benign in ADGRE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). AlphaMissense: likely pathogenic (0.8001); Very rare (popmax 0.00247%, afr).

How common is ADGRE2 p.Cys147Phe (c.440G>T) in the general population?

ADGRE2 p.Cys147Phe (c.440G>T) is very rare (popmax 0.00247%, afr) (gnomAD).

What do computational predictors say about ADGRE2 p.Cys147Phe (c.440G>T)?

AlphaMissense predicts likely pathogenic (score 0.8001) — an in-silico prediction, not a clinical call.

ADGRE2 p.Cys147Phe

c.440G>T · rs773115202 · VCV1686167

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8001 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00247%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8001	likely pathogenic · top 7% in ADGRE2
REVEL	0.814	moderately pathogenic-leaning
SaProt	LLR -11.41	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 1.9, phastCons 0.89
Regional constraint	o/e 0.33	constrained · MANE · 105 bp · p 1.2e-05 · regional, not allelic
Overall
CADD	22.2	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 0.00247% African / African-American · 1/40,560 alleles

Overall 0.00101% 1/99,296 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.Cys147Phe
Coding: c.440G>T
MANE Select: NM_013447
dbSNP: rs773115202
Type: single nucleotide variant
Location: chr19:14767025 (GRCh38)
Gene constraint: LOEUF 1.028 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.44 · 3 PDB
Residue 147: the egf-like 3; 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-cys147phe (accessed [today's date]).

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