ADGRL1 p.Ser366=
c.1098C>T · VCV4688798
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00667%, 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 -4 | |
| Overall | ||
| CADD | 2.874 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00667%
African / African-American · 5/74,932 alleles
Filtering AF
0.00255%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00161%
Overall
0.00186%
30/1,614,068 alleles · very rare
exomes 26/1,461,856 · genomes 4/152,212 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00667% | 14,986 |
| East Asian | 0.00223% | 44,890 |
| European (non-Finnish) | 0.00195% | 51,305 |
| South Asian | 0.0011% | 91,094 |
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.Ser366=
- Coding
- c.1098C>T
- MANE Select
- NM_014921
- Type
- single nucleotide variant
- Location
- chr19:14162703 (GRCh38)
- Gene constraint
- LOEUF 0.302 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 70.63
- Residue 366
- the olfactomedin-like domain; 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-ser366 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown