GP1BA p.Pro421=
c.1263G>A · rs774943025 · VCV3032370
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0372%, afr)
Conditions
1
GP1BA-related disorder
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 -20 | GERP -2.5 |
| Overall | ||
| CADD | 1.551 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0372%
African / African-American · 10/26,846 alleles
Filtering AF
0.0201%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0153%
Overall
0.00292%
27/923,824 alleles · ultra-rare
exomes 23/905,608 · genomes 4/18,216 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0372% | 2,685 |
| Remaining individualsnot grpmax-eligible | 0.00261% | 38,260 |
| South Asian | 0.0022% | 45,500 |
| European (non-Finnish) | 0.00208% | 48,109 |
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
- GP1BA
- Protein
- p.Pro421=
- Coding
- c.1263G>A
- MANE Select
- NM_000173
- dbSNP
- rs774943025
- Type
- single nucleotide variant
- Location
- chr17:4933867 (GRCh38)
- Gene constraint
- LOEUF 1.289 · pLI 0.10 (gnomAD)
- Structure
- AlphaFold pLDDT 64.65 · 22 PDB
- Residue 421
- the 'disordered' region
Disease context
GP1BA-related disorder
Similar variants
- GP1BA p.Pro421Leu Likely benign ★★ ⚠ same residue
- GP1BA p.Ala172Val Pathogenic ★★ ⚠ same condition
- GP1BA p.Gly249Val Pathogenic/Likely pathogenic ★★ same condition
- GP1BA p.Leu83Phe Likely pathogenic ★★ ⚠ same condition
- GP1BA p.Met255Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
- GP1BA p.Val31Glu Uncertain significance ★★ ⚠ same condition
- GP1BA p.Asn198Ser Likely pathogenic ★ same condition
- GP1BA p.Cys33Gly Likely pathogenic ★ same condition
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/gp1ba-p-pro421 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown