C2 p.Glu116=
c.348G>A · rs1183835316 · VCV2415298
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000424%, nfe)
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 1.3 | GERP -3.8, phastCons 1 |
| Overall | ||
| CADD | 5.792 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000424%
European (non-Finnish) · 5/1,180,054 alleles
Filtering AF
0.000124%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9e-05%
Overall
0.00031%
5/1,614,128 alleles · very rare
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
- C2
- Protein
- p.Glu116=
- Coding
- c.348G>A
- MANE Select
- NM_000063
- dbSNP
- rs1183835316
- Type
- single nucleotide variant
- Location
- chr6:31928823 (GRCh38)
- Gene constraint
- LOEUF 0.909 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.61 · 14 PDB
- Residue 116
- a disulfide bond; the sushi 2 domain; a β-strand
Similar variants
- C2 p.Glu116Lys Uncertain significance ★ ⚠ same residue
- C2 c.1902+5G>A Uncertain significance ★★ same type
- C2 c.2029+5G>A Uncertain significance ★★ same type
- C2 p.Ala363Thr Uncertain significance ★★ ⚠ same type
- C2 p.Ala682Glu Uncertain significance ★★ ⚠ same type
- C2 p.Arg124Gln Uncertain significance ★★ ⚠ same type
- C2 p.Arg129His Uncertain significance ★★ ⚠ same type
- C2 p.Arg174Cys 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/c2-p-glu116 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown