PIGS p.Ser453=
c.1359C>T · VCV4823586
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.103%, amr)
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 5.8 | GERP -0.36, phastCons 1 |
| Overall | ||
| CADD | 12.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.103%
Admixed American · 62/59,980 alleles
Filtering AF
0.0827%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0752%
Overall
0.00403%
65/1,614,040 alleles · rare
exomes 61/1,461,892 · genomes 4/152,148 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.103% | 967 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,244 |
| European (non-Finnish) | 8.47e-05% | 1,180,040 |
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.Ser453=
- Coding
- c.1359C>T
- MANE Select
- NM_033198
- Type
- single nucleotide variant
- Location
- chr17:28554884 (GRCh38)
- Gene constraint
- LOEUF 0.76 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.48 · 4 PDB
- Residue 453
- 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)
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-ser453 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown