ADGRG1 p.Ala397=
c.1191C>T · rs1367685651 · VCV499428
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000848%, 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 -7.7 | GERP -3.1 |
| Overall | ||
| CADD | 2.33 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000848%
European (non-Finnish) · 10/1,179,934 alleles
Filtering AF
0.000429%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000312%
Overall
0.00062%
10/1,613,876 alleles · very rare
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
- ADGRG1
- Protein
- p.Ala397=
- Coding
- c.1191C>T
- MANE Select
- NM_201525
- dbSNP
- rs1367685651
- Type
- single nucleotide variant
- Location
- chr16:57657396 (GRCh38)
- Gene constraint
- LOEUF 0.871 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 78.29 · 2 PDB
- Residue 397
- the 'stachel' region; a UniProt-annotated variant site (in cdcbm14a); an α-helix
Similar variants
- ADGRG1 p.Ala397Thr Uncertain significance ★ ⚠ same residue
- ADGRG1 c.1933+1G>T Pathogenic/Likely pathogenic ★★ same type
- ADGRG1 c.488-2A>G Likely pathogenic ★★ same type
- ADGRG1 c.620+1G>A Pathogenic/Likely pathogenic ★★ same type
- ADGRG1 p.Arg271Ter Pathogenic ★★ same type
- ADGRG1 p.Arg38Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- ADGRG1 p.Arg470Ter Pathogenic ★★ same type
- ADGRG1 p.Arg496Ter Pathogenic ★★ 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/adgrg1-p-ala397 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown