AGBL5 p.Ala834=
c.2502C>G · rs748546298 · VCV1160402
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0454%, afr)
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 -5.4 | GERP -4.7 |
| Overall | ||
| CADD | 1.203 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0454%
African / African-American · 34/74,906 alleles
Filtering AF
0.0334%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0292%
Overall
0.00236%
38/1,613,226 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0454% | 2,203 |
| Admixed American | 0.00333% | 29,987 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,223 |
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.Ala834=
- Coding
- c.2502C>G
- MANE Select
- NM_021831
- dbSNP
- rs748546298
- Type
- single nucleotide variant
- Location
- chr2:27070104 (GRCh38)
- Gene constraint
- LOEUF 0.709 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.36 · 10 PDB
- Residue 834
- 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.Ala834Ser Uncertain significance ★★ ⚠ same residue
- AGBL5 p.Ala834Thr 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-ala834 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown