AFG2B p.Pro728=
c.2184G>A · rs773984786 · VCV2645307
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0452%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.373 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -5.9 | GERP -3.8 |
| Overall | ||
| CADD | 0.083 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0452%
Admixed American · 27/59,734 alleles
Filtering AF
0.0318%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0274%
Overall
0.00595%
96/1,612,820 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0452% | 2,212 |
| Middle Eastern | 0.0165% | 6,048 |
| East Asian | 0.0067% | 14,936 |
| South Asian | 0.0066% | 15,144 |
| European (non-Finnish) | 0.00475% | 21,065 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,221 |
| African / African-American | 0.00134% | 74,800 |
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
- AFG2B
- Protein
- p.Pro728=
- Coding
- c.2184G>A
- MANE Select
- NM_024063
- dbSNP
- rs773984786
- Type
- single nucleotide variant
- Location
- chr15:45421132 (GRCh38)
- Structure
- AlphaFold pLDDT 77.37 · 2 PDB
- Residue 728
- a UniProt-annotated variant site (in nedhls)
Similar variants
- AFG2B p.Pro728Leu Uncertain significance ★ ⚠ same residue
- AFG2B p.Ile466Met Pathogenic/Likely pathogenic ★★ ⚠ same type
- AFG2B p.Thr400Ile Pathogenic/Likely pathogenic ★★ same type
- AFG2B p.Arg288Pro Uncertain significance ★★ ⚠ same type
- AFG2B p.Arg28Cys Uncertain significance ★★ ⚠ same type
- AFG2B p.Phe71Leu Uncertain significance ★★ ⚠ same type
- AFG2B p.Pro558Arg Uncertain significance ★★ ⚠ same type
- AFG2B p.Ser333Ile 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/afg2b-p-pro728 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown