GPAA1 p.Pro553=
c.1659G>A · rs367686000 · VCV1922111
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0132%, sas)
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 -3.5 | GERP -3.5 |
| Overall | ||
| CADD | 0.595 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0132%
South Asian · 12/91,032 alleles
Filtering AF
0.00751%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00593%
Overall
0.00158%
23/1,457,292 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0132% | 7,586 |
| Admixed American | 0.00333% | 29,997 |
| African / African-American | 0.00267% | 37,514 |
| European (non-Finnish) | 0.000594% | 168,458 |
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.Pro553=
- Coding
- c.1659G>A
- MANE Select
- NM_003801
- dbSNP
- rs367686000
- Type
- single nucleotide variant
- Location
- chr8:144085918 (GRCh38)
- Gene constraint
- LOEUF 1.077 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.48 · 4 PDB
- Residue 553
- an α-helix
Similar variants
- GPAA1 p.Pro553Leu Uncertain significance ★★ ⚠ same residue
- GPAA1 p.Pro553Thr 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
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-pro553 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown