SERPING1 p.Ala140=
c.420C>T · rs1304088976 · VCV2907714
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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 -2.5 | GERP -4.9 |
| Overall | ||
| CADD | 2.086 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,058 alleles
Filtering AF
0.00103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00083%
Overall
0.00149%
24/1,614,114 alleles · ultra-rare
exomes 23/1,461,882 · genomes 1/152,232 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,058 |
| East Asian | 0.00446% | 22,443 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,252 |
| European (non-Finnish) | 0.00161% | 62,106 |
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.Ala140=
- Coding
- c.420C>T
- MANE Select
- NM_000062
- dbSNP
- rs1304088976
- Type
- single nucleotide variant
- Location
- chr11:57600247 (GRCh38)
- Gene constraint
- LOEUF 0.278 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.63 · 5 PDB
- Residue 140
- an α-helix
Similar variants
- SERPING1 p.Ala140Gly Uncertain significance ★ ⚠ 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-ala140 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown