ADGRL1 p.Pro486=
c.1458G>A · VCV4681366
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.096%, afr)
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 -15 | |
| Overall | ||
| CADD | 1.322 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.096%
African / African-American · 71/73,938 alleles
Filtering AF
0.0781%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0714%
Overall
0.0308%
487/1,580,290 alleles · ultra-rare
exomes 423/1,428,430 · genomes 64/151,860 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.096% | 1,041 |
| European (non-Finnish) | 0.0338% | 2,958 |
| Remaining individualsnot grpmax-eligible | 0.0196% | 5,098 |
| Middle Eastern | 0.0173% | 5,796 |
| South Asian | 0.00582% | 17,176 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0036% | 27,742 |
| Admixed American | 0.00349% | 28,650 |
| East Asian | 0.0023% | 43,468 |
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
- ADGRL1
- Protein
- p.Pro486=
- Coding
- c.1458G>A
- MANE Select
- NM_014921
- Type
- single nucleotide variant
- Location
- chr19:14161364 (GRCh38)
- Gene constraint
- LOEUF 0.302 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 70.63
- Residue 486
- a UniProt-annotated variant site (in dedbanp; loss of protein expression; loss of g protein-coupled receptor signaling); a UniProt-annotated variant site (in dedbanp)
Similar variants
- ADGRL1 p.Arg1108His Uncertain significance ★★ ⚠ same type
- ADGRL1 p.Arg1387Gln Uncertain significance ★★ ⚠ same type
- ADGRL1 p.Arg178Cys Uncertain significance ★★ ⚠ same type
- ADGRL1 p.Arg27Gln Uncertain significance ★★ same type
- ADGRL1 p.Arg338His Uncertain significance ★★ ⚠ same type
- ADGRL1 p.Arg460Trp Uncertain significance ★★ ⚠ same type
- ADGRL1 p.Arg49Trp Uncertain significance ★★ ⚠ same type
- ADGRL1 p.Arg557Trp 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/adgrl1-p-pro486 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown