Is ADGRE2 p.Ile511Val (c.1531A>G) pathogenic?

ADGRE2 p.Ile511Val (c.1531A>G) is classified Benign in ADGRE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). AlphaMissense: likely benign (0.0834); Very rare (popmax 0.000254%, nfe).

How common is ADGRE2 p.Ile511Val (c.1531A>G) in the general population?

ADGRE2 p.Ile511Val (c.1531A>G) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about ADGRE2 p.Ile511Val (c.1531A>G)?

AlphaMissense predicts likely benign (score 0.0834) — an in-silico prediction, not a clinical call.

ADGRE2 p.Ile511Val

c.1531A>G · rs775421833 · VCV1685541

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0834 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0834	likely benign
REVEL	0.272	benign-leaning
SaProt	LLR -5.04	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 0.15	GERP -0.53, phastCons 0.012
Regional constraint	o/e 0.82	unconstrained · MANE · 29 kb · p 2.6e-06 · regional, not allelic
Overall
CADD	16.25	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 0.000254% European (non-Finnish) · 3/1,180,028 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,856 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.Ile511Val
Coding: c.1531A>G
MANE Select: NM_013447
dbSNP: rs775421833
Type: single nucleotide variant
Location: chr19:14755013 (GRCh38)
Gene constraint: LOEUF 1.028 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.44 · 3 PDB
Residue 511: the gain-b domain; the 'gps' region; 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-ile511val (accessed [today's date]).

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