AGBL5 p.Pro417=
c.1251T>G · rs1426311632 · VCV1535561
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00288%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.8 | GERP -3.5 |
| Overall | ||
| CADD | 4.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00288%
European (non-Finnish) · 34/1,180,026 alleles
Filtering AF
0.00207%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00183%
Overall
0.00211%
34/1,614,088 alleles · very rare
exomes 32/1,461,868 · genomes 2/152,220 · 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
- AGBL5
- Protein
- p.Pro417=
- Coding
- c.1251T>G
- MANE Select
- NM_021831
- dbSNP
- rs1426311632
- Type
- single nucleotide variant
- Location
- chr2:27056024 (GRCh38)
- Gene constraint
- LOEUF 0.709 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.36 · 10 PDB
- Residue 417
- the peptidase m14 domain; a UniProt-annotated variant site (found in patients with a usher-like phenotype encompassing rp and hearing loss; likely pathogenic)
Similar variants
- AGBL5 p.Pro417fs Pathogenic ★ same residue
- AGBL5 p.Arg220Ter Pathogenic ★★ same type
- AGBL5 p.Arg487Ter Pathogenic ★★ same type
- AGBL5 p.Trp592Ter Pathogenic ★★ same type
- AGBL5 p.Tyr485Ter Pathogenic/Likely pathogenic ★★ same type
- AGBL5 c.2355+4A>G Uncertain significance ★★ same type
- AGBL5 c.551+5C>A Uncertain significance ★★ same type
- AGBL5 p.Ala530Thr 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/agbl5-p-pro417 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown