Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.49%, nfe)
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 -9.8 | GERP -5.2 |
| Overall | ||
| CADD | 1.148 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.49%
European (non-Finnish) · 17,635/1,179,978 alleles
Filtering AF
1.48%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.47%
Overall
1.19%
19,148/1,614,010 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 1.49% | 67 |
| Remaining individualsnot grpmax-eligible | 1.06% | 94 |
| Admixed American | 0.343% | 291 |
| South Asian | 0.309% | 324 |
| Finnishnot grpmax-eligible | 0.276% | 362 |
| African / African-American | 0.217% | 460 |
| Middle Eastern | 0.214% | 466 |
| Amishnot grpmax-eligible | 0.11% | 910 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0338% | 2,961 |
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
- Protein
- p.Ala1040=
- Coding
- c.3120G>A
- MANE Select
- NM_145290
- dbSNP
- rs12700
- Type
- single nucleotide variant
- Location
- chr4:22388551 (GRCh38)
- Gene constraint
- LOEUF 0.607 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.20
Similar variants
- ADGRA3 p.Ala1040Val Uncertain significance ★ ⚠ same residue
- 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
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-p-ala1040 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown