AGBL5 p.Arg863Ser
c.2589G>C · rs376506451 · VCV2300989
Computational evidence
| Protein change | ||
| AlphaMissense | 0.0984 | likely benign |
|---|---|---|
| REVEL | 0.032 | moderately benign-leaning |
| SaProt | LLR -5.24 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Pangolin | Δ0.26 | gain · loss 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 5.9 | GERP 0.18, phastCons 1 |
| Regional constraint | o/e 1.01 | unconstrained · MANE · 13 kb · p 0.75 · regional, not allelic |
| Overall | ||
| CADD | 17.29 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| European (non-Finnish) | 0.00203% | 49,168 |
| African / African-American | 0.00134% | 74,906 |
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.Arg863Ser
- Coding
- c.2589G>C
- MANE Select
- NM_021831
- dbSNP
- rs376506451
- Type
- single nucleotide variant
- Location
- chr2:27070191 (GRCh38)
- Gene constraint
- LOEUF 0.709 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.36 · 10 PDB
- Residue 863
- 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)
Similar variants
- 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
- AGBL5 p.Arg204His 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-arg863ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown