AGBL5 p.Ser737del
c.2210_2212del · rs778210164 · VCV955350
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0329%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 2.5, phastCons 1 |
| Overall | ||
| CADD | 16.89 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0329%
Middle Eastern · 2/6,084 alleles
Filtering AF
0.0166%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0137%
Overall
0.00143%
23/1,613,884 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0329% | 3,042 |
| African / African-American | 0.0254% | 3,941 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
| European (non-Finnish) | 8.47e-05% | 1,179,976 |
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.Ser737del
- Coding
- c.2210_2212del
- MANE Select
- NM_021831
- dbSNP
- rs778210164
- Type
- Deletion
- Location
- chr2:27067612 (GRCh38)
- Gene constraint
- LOEUF 0.709 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.36 · 10 PDB
- Residue 737
- 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 c.2090-18_2090-16del Benign/Likely benign ★★ same type
- AGBL5 c.2090-7del Likely benign ★★ same type
- AGBL5 c.552-9del Benign/Likely benign ★★ same type
- AGBL5 c.1874+2_1874+5del Likely pathogenic ★ same type
- AGBL5 p.Gln372fs Likely pathogenic ★ same type
- AGBL5 p.Gln708fs Likely pathogenic ★ same type
- AGBL5 p.Gly105fs Likely pathogenic ★ same type
- AGBL5 p.Gly264fs Pathogenic ★ 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-ser737del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown