PIGS p.Pro505=
c.1515G>A · rs373354668 · VCV2570979
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0677%, nfe)
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 -0.11 | GERP -3.3, phastCons 0.11 |
| Overall | ||
| CADD | 11.51 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0677%
European (non-Finnish) · 799/1,180,020 alleles
Filtering AF
0.0638%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0622%
Overall
0.0522%
843/1,614,116 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0677% | 1,477 |
| Remaining individualsnot grpmax-eligible | 0.048% | 2,084 |
| African / African-American | 0.0133% | 7,501 |
| Admixed American | 0.005% | 20,005 |
| Finnishnot grpmax-eligible | 0.00156% | 64,020 |
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
- PIGS
- Protein
- p.Pro505=
- Coding
- c.1515G>A
- MANE Select
- NM_033198
- dbSNP
- rs373354668
- Type
- single nucleotide variant
- Location
- chr17:28554373 (GRCh38)
- Gene constraint
- LOEUF 0.76 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.48 · 4 PDB
- Residue 505
- a UniProt-annotated variant site (in gpibd18; almost complete loss of function; when tested in pigs-knockout cells, mediates only very partial restoration of gpi-anchored protein expression at the cell surface; strong decrease in protein level, possibly due to nonsense-mediated mrna decay); an α-helix
Similar variants
- PIGS p.Arg15Trp Uncertain significance ★★ ⚠ same type
- PIGS p.Arg176Trp Uncertain significance ★★ ⚠ same type
- PIGS p.Arg355Cys Uncertain significance ★★ ⚠ same type
- PIGS p.Pro402Ser Uncertain significance ★★ ⚠ same type
- PIGS p.Ser224Thr Uncertain significance ★★ ⚠ same type
- PIGS p.Tyr522Cys Uncertain significance ★★ ⚠ same type
- PIGS p.Val146Met Uncertain significance ★★ ⚠ same type
- PIGS c.1080+15A>G Likely benign ★★ 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/pigs-p-pro505 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown