AGBL5 p.Ala486=
c.1458C>A · rs369251730 · VCV772840
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.104%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP 0.36, phastCons 1 |
| Overall | ||
| CADD | 13.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.104%
South Asian · 95/91,036 alleles
Filtering AF
0.0873%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.081%
Overall
0.00806%
130/1,613,758 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.104% | 958 |
| Middle Eastern | 0.0825% | 1,212 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,495 |
| European (non-Finnish) | 0.00203% | 49,159 |
| Admixed American | 0.00167% | 59,998 |
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.Ala486=
- Coding
- c.1458C>A
- MANE Select
- NM_021831
- dbSNP
- rs369251730
- Type
- single nucleotide variant
- Location
- chr2:27056715 (GRCh38)
- Gene constraint
- LOEUF 0.709 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.36 · 10 PDB
- Residue 486
- 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.Ala486Gly Uncertain significance ★ ⚠ same residue
- AGBL5 p.Ala486Val Uncertain significance ★ ⚠ 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
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-ala486 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown