SERPING1 p.Ala465=
c.1395C>T · rs776423329 · VCV1529859
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0267%, afr)
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 0.21 | GERP 2, phastCons 0.97 |
| Overall | ||
| CADD | 9.543 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0267%
African / African-American · 20/74,932 alleles
Filtering AF
0.0177%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0147%
Overall
0.0013%
21/1,613,994 alleles · ultra-rare
exomes 6/1,461,796 · genomes 15/152,198 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0267% | 3,747 |
| 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.Ala465=
- Coding
- c.1395C>T
- MANE Select
- NM_000062
- dbSNP
- rs776423329
- Type
- single nucleotide variant
- Location
- chr11:57614473 (GRCh38)
- Gene constraint
- LOEUF 0.278 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.63 · 5 PDB
- Residue 465
- a functional site (reactive bond for chymotrypsin); a UniProt-annotated variant site (in hae1; phenotype consistent with hereditary angioedema type 2)
Similar variants
- SERPING1 p.Ala465Val Uncertain significance ★ ⚠ same residue
- SERPING1 p.Ala465fs Likely pathogenic ★ 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
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-ala465 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown