SERPING1 p.Pro66=
c.198G>A · rs774845024 · VCV2069124
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.045%, sas)
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 -3.8 | GERP -3.2 |
| Overall | ||
| CADD | 0.651 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.045%
South Asian · 41/91,066 alleles
Filtering AF
0.0341%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0302%
Overall
0.00638%
103/1,613,998 alleles · ultra-rare
exomes 90/1,461,878 · genomes 13/152,120 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.045% | 2,221 |
| Middle Eastern | 0.0165% | 6,062 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,500 |
| European (non-Finnish) | 0.00441% | 22,692 |
| African / African-American | 0.004% | 24,991 |
| Admixed American | 0.00167% | 59,996 |
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
- SERPING1
- Protein
- p.Pro66=
- Coding
- c.198G>A
- MANE Select
- NM_000062
- dbSNP
- rs774845024
- Type
- single nucleotide variant
- Location
- chr11:57600025 (GRCh38)
- Gene constraint
- LOEUF 0.278 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.63 · 5 PDB
- Residue 66
- the 'disordered' region
Similar variants
- SERPING1 p.Pro66Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- SERPING1 c.1030-1G>T Pathogenic ★★ same type
- SERPING1 c.51+1G>T Pathogenic ★★ same type
- SERPING1 c.51+3A>C Pathogenic/Likely pathogenic ★★ same type
- SERPING1 c.51+3A>G Pathogenic ★★ same type
- SERPING1 c.52-1G>A Pathogenic ★★ same type
- SERPING1 c.550+1G>A Pathogenic ★★ same type
- SERPING1 c.551-1G>C Pathogenic/Likely pathogenic ★★ 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/serping1-p-pro66 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown