AGBL5 p.Pro422=
c.1266C>A · rs373237623 · VCV1664355
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00737%, nfe)
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 -6.1 | GERP -5 |
| Overall | ||
| CADD | 0.668 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00737%
European (non-Finnish) · 87/1,180,046 alleles
Filtering AF
0.00605%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00565%
Overall
0.00601%
97/1,614,092 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00737% | 13,564 |
| African / African-American | 0.00534% | 18,730 |
| Admixed American | 0.00333% | 30,005 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,245 |
| East Asian | 0.00223% | 44,904 |
| South Asian | 0.0011% | 91,084 |
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.Pro422=
- Coding
- c.1266C>A
- MANE Select
- NM_021831
- dbSNP
- rs373237623
- Type
- single nucleotide variant
- Location
- chr2:27056039 (GRCh38)
- Gene constraint
- LOEUF 0.709 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.36 · 10 PDB
- Residue 422
- 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 turn
Similar variants
- AGBL5 p.Pro422Ala Uncertain significance ★★ ⚠ same residue
- AGBL5 p.Pro422Arg Uncertain significance ★★ ⚠ same residue
- AGBL5 p.Pro422His Uncertain significance ★★ ⚠ same residue
- AGBL5 p.Pro422Leu Uncertain significance ★★ ⚠ same residue
- AGBL5 p.Pro422Ser Uncertain significance ★★ ⚠ same residue
- AGBL5 p.Pro422Thr Uncertain significance ★★ ⚠ same residue
- AGBL5 p.Arg220Ter Pathogenic ★★ same type
- AGBL5 p.Arg487Ter 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-pro422 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown