AGBL5 p.Pro543=
c.1629G>A · rs769821257 · VCV2053475
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0184%, amr)
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 -3.7 | GERP -5 |
| Overall | ||
| CADD | 5.194 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0184%
Admixed American · 11/59,902 alleles
Filtering AF
0.0102%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00796%
Overall
0.00186%
30/1,613,230 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0184% | 5,446 |
| African / African-American | 0.00668% | 14,968 |
| East Asian | 0.00446% | 22,424 |
| South Asian | 0.0044% | 22,739 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,446 |
| European (non-Finnish) | 0.000593% | 168,525 |
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.Pro543=
- Coding
- c.1629G>A
- MANE Select
- NM_021831
- dbSNP
- rs769821257
- Type
- single nucleotide variant
- Location
- chr2:27057396 (GRCh38)
- Gene constraint
- LOEUF 0.709 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.36 · 10 PDB
- Residue 543
- the peptidase m14 domain; 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); an α-helix
Similar variants
- AGBL5 p.Pro543Leu 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
- AGBL5 p.Ala530Thr 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-pro543 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown