ADGRV1 p.Pro780=
c.2340T>C · rs1486650258 · VCV905576
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 0.000593%, nfe)
Conditions
1
Usher syndrome type 2C
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.078 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.052 | GERP -1.9, phastCons 0.001 |
| Overall | ||
| CADD | 11.14 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000593%
European (non-Finnish) · 7/1,179,598 alleles
Filtering AF
0.000247%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000159%
Overall
0.000434%
7/1,613,460 alleles · very rare
exomes 5/1,461,270 · genomes 2/152,190 · joint denominator
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
- ADGRV1
- Protein
- p.Pro780=
- Coding
- c.2340T>C
- MANE Select
- NM_032119
- dbSNP
- rs1486650258
- Type
- single nucleotide variant
- Location
- chr5:90642735 (GRCh38)
- Gene constraint
- LOEUF 0.637 · pLI <0.01 (gnomAD)
- Residue 780
- the calx-beta 6 domain
Similar variants
- ADGRV1 p.Pro780Ser Uncertain significance ★ ⚠ same residue
- ADGRV1 p.Pro780Thr Likely benign ★ same residue
- ADGRV1 c.10974+1G>A Likely pathogenic ★★ same condition
- ADGRV1 c.11757+2T>C Likely pathogenic ★★ same condition
- ADGRV1 c.1239-1G>T Pathogenic/Likely pathogenic ★★ same condition
- ADGRV1 c.13232-1G>A Pathogenic/Likely pathogenic ★★ same condition
- ADGRV1 c.14972+1G>T Pathogenic/Likely pathogenic ★★ same condition
- ADGRV1 c.14973-2A>G Pathogenic/Likely pathogenic ★★ same condition
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/adgrv1-p-pro780 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown