ADGRA3 c.2357+8A>G
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0495%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +8 | near-intronic (+8 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -4.3 | GERP -4.1 |
| Non-coding constraint | Z 1.59 | 1 kb window · o/e 0.89 · regional · uncalibrated |
| Overall | ||
| CADD | 0.066 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0495%
African / African-American · 37/74,686 alleles
Filtering AF
0.0369%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0326%
Overall
0.00323%
52/1,609,750 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0495% | 2,019 |
| Admixed American | 0.0017% | 58,956 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,336 |
| European (non-Finnish) | 0.0011% | 90,677 |
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
- ADGRA3
- Coding
- c.2357+8A>G
- MANE Select
- NM_145290
- dbSNP
- rs370263563
- Type
- single nucleotide variant
- Location
- chr4:22402667 (GRCh38)
- Gene constraint
- LOEUF 0.607 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.20
Similar variants
- ADGRA3 p.Ala1008Val Uncertain significance ★★ ⚠ same type
- ADGRA3 p.Ala1120Val Uncertain significance ★★ ⚠ same type
- ADGRA3 p.Ala1127Ser Uncertain significance ★★ ⚠ same type
- ADGRA3 p.Ala177Val Uncertain significance ★★ ⚠ same type
- ADGRA3 p.Ala26Pro Uncertain significance ★★ ⚠ same type
- ADGRA3 p.Ala316Pro Uncertain significance ★★ ⚠ same type
- ADGRA3 p.Ala37Gly Uncertain significance ★★ ⚠ same type
- ADGRA3 p.Ala407Thr 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/adgra3-c-2357-plus-8a-g (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown