GPAA1 p.Ser98=
c.294A>G · rs539004909 · VCV2418376
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0713%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.55 | donor loss, 4 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.4 | GERP -3.5 |
| Overall | ||
| CADD | 9.989 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0713%
East Asian · 32/44,854 alleles
Filtering AF
0.0519%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0453%
Overall
0.00223%
36/1,613,750 alleles · ultra-rare
exomes 31/1,461,526 · genomes 5/152,224 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0713% | 1,402 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,835 |
| European (non-Finnish) | 8.47e-05% | 1,179,990 |
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
- GPAA1
- Protein
- p.Ser98=
- Coding
- c.294A>G
- MANE Select
- NM_003801
- dbSNP
- rs539004909
- Type
- single nucleotide variant
- Location
- chr8:144083428 (GRCh38)
- Gene constraint
- LOEUF 1.077 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.48 · 4 PDB
- Residue 98
- an α-helix
Similar variants
- GPAA1 p.Ser98Leu Uncertain significance ★ ⚠ same residue
- GPAA1 c.1165-1C>T Likely pathogenic ★★ same type
- GPAA1 c.366+1G>A Likely pathogenic ★★ same type
- GPAA1 c.616+1G>T Likely pathogenic ★★ same type
- GPAA1 p.Arg215Ter Pathogenic/Likely pathogenic ★★ same type
- GPAA1 p.Leu291Pro Likely pathogenic ★★ same type
- GPAA1 p.Ser419Ter Pathogenic/Likely pathogenic ★★ same type
- GPAA1 c.1164+1A>G 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/gpaa1-p-ser98 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown