GPAA1 p.Ser154=
c.462T>C · rs782209028 · VCV1575728
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0228%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.2 | GERP -3.8 |
| Overall | ||
| CADD | 4.399 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0228%
European (non-Finnish) · 269/1,179,548 alleles
Filtering AF
0.0205%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0196%
Overall
0.0174%
280/1,609,676 alleles · ultra-rare
exomes 275/1,457,508 · genomes 5/152,168 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0228% | 4,385 |
| Admixed American | 0.00667% | 14,999 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,807 |
| African / African-American | 0.00401% | 24,968 |
| South Asian | 0.0011% | 91,070 |
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.Ser154=
- Coding
- c.462T>C
- MANE Select
- NM_003801
- dbSNP
- rs782209028
- Type
- single nucleotide variant
- Location
- chr8:144083809 (GRCh38)
- Gene constraint
- LOEUF 1.077 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.48 · 4 PDB
- Residue 154
- a β-strand
Similar variants
- GPAA1 p.Ser154fs Pathogenic/Likely pathogenic ★★ 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-ser154 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown