PIGS p.Pro335=
c.1005G>A · rs760728308 · VCV2647584
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0134%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.043 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -14 | GERP -3.6 |
| Overall | ||
| CADD | 0.982 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0134%
East Asian · 6/44,876 alleles
Filtering AF
0.00579%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00394%
Overall
0.00109%
16/1,461,862 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0134% | 7,479 |
| South Asian | 0.0011% | 91,078 |
| European (non-Finnish) | 0.000763% | 131,113 |
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.Pro335=
- Coding
- c.1005G>A
- MANE Select
- NM_033198
- dbSNP
- rs760728308
- Type
- single nucleotide variant
- Location
- chr17:28556902 (GRCh38)
- Gene constraint
- LOEUF 0.76 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.48 · 4 PDB
- Residue 335
- 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); a β-strand
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-pro335 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown