AGBL5 p.Arg699Gln
c.2096G>A · rs778548414 · VCV1464505
Computational evidence
| Protein change | ||
| AlphaMissense | 0.1379 | likely benign |
|---|---|---|
| REVEL | 0.119 | moderately benign-leaning |
| SaProt | LLR -6.42 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2.5, phastCons 1 |
| Regional constraint | o/e 1.01 | unconstrained · MANE · 13 kb · p 0.75 · regional, not allelic |
| Overall | ||
| CADD | 28.5 | 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 |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,833 |
| East Asiangrpmax | 0.00446% | 22,422 |
| African / African-American | 0.004% | 24,982 |
| Admixed American | 0.00167% | 59,994 |
| Finnishnot grpmax-eligible | 0.00156% | 63,978 |
| European (non-Finnish) | 0.00127% | 78,655 |
| South Asian | 0.0011% | 91,076 |
Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Arg699Gln
- Coding
- c.2096G>A
- MANE Select
- NM_021831
- dbSNP
- rs778548414
- Type
- single nucleotide variant
- Location
- chr2:27067500 (GRCh38)
- Gene constraint
- LOEUF 0.709 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.36 · 10 PDB
- Residue 699
- 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); the 'disordered' region
Similar variants
- AGBL5 p.Trp592Ter Pathogenic ★★ same condition
- 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-arg699gln (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown