PIGV p.Pro333=
c.999A>C · rs764422244 · VCV744288
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0022%, 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 -0.69 | GERP -1.6 |
| Overall | ||
| CADD | 7.078 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0022%
European (non-Finnish) · 26/1,180,044 alleles
Filtering AF
0.00153%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0013%
Overall
0.00167%
27/1,614,100 alleles · very rare
exomes 24/1,461,880 · genomes 3/152,220 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0022% | 45,386 |
| Admixed American | 0.00167% | 60,004 |
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
- PIGV
- Protein
- p.Pro333=
- Coding
- c.999A>C
- MANE Select
- NM_017837
- dbSNP
- rs764422244
- Type
- single nucleotide variant
- Location
- chr1:26795033 (GRCh38)
- Gene constraint
- LOEUF 0.902 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.22
Similar variants
- PIGV p.Pro333Ser Uncertain significance ★ ⚠ same residue
- PIGV p.Pro333fs Uncertain significance same residue
- PIGV p.Ala341Glu Pathogenic/Likely pathogenic ★★ same type
- PIGV p.Ala418Asp Likely pathogenic ★★ same type
- PIGV p.Arg19Cys Likely pathogenic ★★ ⚠ same type
- PIGV p.Arg203Cys Pathogenic/Likely pathogenic ★★ same type
- PIGV p.Cys156Tyr Pathogenic/Likely pathogenic ★★ same type
- PIGV p.Ala386Thr 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/pigv-p-pro333 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown