AGBL5 p.Pro628=
c.1884T>C · rs780021648 · VCV1147306
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00836%, 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 -4.7 | GERP -4.7 |
| Overall | ||
| CADD | 3.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00836%
Admixed American · 5/59,774 alleles
Filtering AF
0.00324%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00207%
Overall
0.000496%
8/1,613,150 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00836% | 11,955 |
| African / African-American | 0.00134% | 74,778 |
| European (non-Finnish) | 0.00017% | 589,797 |
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.Pro628=
- Coding
- c.1884T>C
- MANE Select
- NM_021831
- dbSNP
- rs780021648
- Type
- single nucleotide variant
- Location
- chr2:27059199 (GRCh38)
- Gene constraint
- LOEUF 0.709 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.36 · 10 PDB
- Residue 628
- 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.Pro628Leu Conflicting classifications of pathogenicity ★ 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-pro628 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown