AAGAB p.Ser218=
c.654C>T · VCV4738033
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0986%, mid)
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 0.43 | GERP -2.8, phastCons 0.98 |
| Overall | ||
| CADD | 0.917 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0986%
Middle Eastern · 6/6,084 alleles
Filtering AF
0.0429%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0293%
Overall
0.00155%
25/1,613,956 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0986% | 1,014 |
| African / African-American | 0.016% | 6,240 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,497 |
| Admixed American | 0.00167% | 59,992 |
| European (non-Finnish) | 8.47e-05% | 1,180,004 |
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
- AAGAB
- Protein
- p.Ser218=
- Coding
- c.654C>T
- MANE Select
- NM_024666
- Type
- single nucleotide variant
- Location
- chr15:67208623 (GRCh38)
- Gene constraint
- LOEUF 1.156 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 80.41 · 3 PDB
- Residue 218
- the 'disordered' region
Similar variants
- AAGAB p.Arg124Ter Pathogenic ★★ same type
- AAGAB p.Arg161Ter Pathogenic ★★ same type
- AAGAB p.Gln21Ter Pathogenic ★★ same type
- AAGAB p.Ala74Pro Uncertain significance ★★ ⚠ same type
- AAGAB p.Arg161Gln Uncertain significance ★★ ⚠ same type
- AAGAB p.Leu92Val Uncertain significance ★★ ⚠ same type
- AAGAB c.264+33A>G Benign ★★ same type
- AAGAB c.536-95G>A Benign ★★ 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/aagab-p-ser218 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown