ADGRE1 p.Ser488=
c.1464G>A · rs537322666 · VCV2649147
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00334%, amr)
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 -2.4 | GERP -3.1 |
| Overall | ||
| CADD | 3.176 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00334%
Admixed American · 2/59,820 alleles
Filtering AF
0.000555%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000208%
Overall
0.00031%
5/1,613,058 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00334% | 29,910 |
| South Asian | 0.0011% | 91,034 |
| European (non-Finnish) | 0.00017% | 589,925 |
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
- ADGRE1
- Protein
- p.Ser488=
- Coding
- c.1464G>A
- MANE Select
- NM_001974
- dbSNP
- rs537322666
- Type
- single nucleotide variant
- Location
- chr19:6919591 (GRCh38)
- Gene constraint
- LOEUF 0.951 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.75
- Residue 488
- the gain-b domain
Similar variants
- ADGRE1 c.2382-4C>T Benign ★★ same type
- ADGRE1 p.Arg2Leu Benign ★★ same type
- ADGRE1 p.Pro880Thr Benign ★★ same type
- ADGRE1 p.Thr885Met Benign ★★ ⚠ same type
- ADGRE1 p.Ala177Val Uncertain significance ★ ⚠ same type
- ADGRE1 p.Ala57Val Uncertain significance ★ ⚠ same type
- ADGRE1 p.Ala592Val Uncertain significance ★ ⚠ same type
- ADGRE1 p.Ala620Val 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/adgre1-p-ser488 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown