AGBL5 p.Phe260=
c.780T>C · rs17005799 · VCV783021
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.82%, 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 3.5 | GERP 0.49, phastCons 1 |
| Overall | ||
| CADD | 11.86 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.82%
African / African-American · 3,620/75,058 alleles
Filtering AF
4.69%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.64%
Overall
0.253%
4,085/1,614,220 alleles · low-frequency
exomes 1,960/1,461,876 · genomes 2,125/152,344 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.82% | 21 |
| Admixed American | 0.345% | 290 |
| Remaining individualsnot grpmax-eligible | 0.339% | 295 |
| Middle Eastern | 0.0825% | 1,212 |
| South Asian | 0.0209% | 4,794 |
| European (non-Finnish) | 0.00186% | 53,638 |
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.Phe260=
- Coding
- c.780T>C
- MANE Select
- NM_021831
- dbSNP
- rs17005799
- Type
- single nucleotide variant
- Location
- chr2:27055125 (GRCh38)
- Gene constraint
- LOEUF 0.709 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.36 · 10 PDB
- Residue 260
- the peptidase m14 domain; a UniProt-annotated variant site (found in patients with a usher-like phenotype encompassing rp and hearing loss; likely pathogenic); an α-helix
Similar variants
- 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
- AGBL5 p.Ala530Thr Uncertain significance ★★ ⚠ same type
- AGBL5 p.Ala570Val 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-phe260 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown