AGBL5 p.Arg500His
c.1499G>A · rs201033068 · VCV1485153
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9988 | likely pathogenic · top 4% in AGBL5 |
|---|---|---|
| REVEL | 0.666 | pathogenic-leaning |
| SaProt | LLR -12.67 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.5, phastCons 1 |
| Regional constraint | o/e 0.80 | unconstrained · MANE · 4,357 bp · p 1.1e-07 · regional, not allelic |
| Overall | ||
| CADD | 33.0 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00401% | 24,966 |
| East Asian | 0.00223% | 44,854 |
| Admixed American | 0.00167% | 59,940 |
| European (non-Finnish) | 0.000509% | 196,571 |
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.Arg500His
- Coding
- c.1499G>A
- MANE Select
- NM_021831
- dbSNP
- rs201033068
- Type
- single nucleotide variant
- Location
- chr2:27056756 (GRCh38)
- Gene constraint
- LOEUF 0.709 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.36 · 10 PDB
- Residue 500
- the peptidase m14 domain; a UniProt-annotated variant site (found in patients with a usher-like phenotype encompassing rp and hearing loss; likely pathogenic); a UniProt-annotated variant site (in rp75); an α-helix
Similar variants
- AGBL5 p.Arg500Cys Uncertain significance ★ ⚠ same residue
- AGBL5 p.Ala530Thr Uncertain significance ★★ ⚠ same condition
- AGBL5 p.Arg111Cys Uncertain significance ★★ ⚠ same condition
- AGBL5 p.Arg121His Uncertain significance ★★ ⚠ same condition
- AGBL5 p.Arg147Cys Uncertain significance ★★ ⚠ same condition
- AGBL5 p.Arg147Gly Uncertain significance ★★ ⚠ same condition
- AGBL5 p.Arg147His Uncertain significance ★★ ⚠ same condition
- AGBL5 p.Arg174His Uncertain significance ★★ ⚠ 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/agbl5-p-arg500his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown