GPAA1 p.Ser426=
c.1278G>A · rs782326011 · VCV1644704
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0166%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.61 | acceptor loss, 17 bp away · masked 0 · deltas |
|---|---|---|
| Pangolin | Δ0.54 | loss · gain 0.53 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -4.1 | GERP -3.8 |
| Overall | ||
| CADD | 0.301 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0166%
Middle Eastern · 1/6,010 alleles
Filtering AF
0.00226%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00135%
Overall
0.000561%
9/1,605,168 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0166% | 6,010 |
| Admixed American | 0.0067% | 14,927 |
| East Asian | 0.00224% | 44,708 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,142 |
| South Asian | 0.0011% | 90,582 |
| European (non-Finnish) | 8.5e-05% | 1,175,780 |
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.Ser426=
- Coding
- c.1278G>A
- MANE Select
- NM_003801
- dbSNP
- rs782326011
- Type
- single nucleotide variant
- Location
- chr8:144085306 (GRCh38)
- Gene constraint
- LOEUF 1.077 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.48 · 4 PDB
- Residue 426
- an α-helix
Similar variants
- 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
- GPAA1 c.1451+5G>A 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-ser426 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown