C2 p.Gly466=
c.1398G>A · VCV3633314
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00229%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.116 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.31 | GERP -1.8, phastCons 0.93 |
| Overall | ||
| CADD | 8.21 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00229%
European (non-Finnish) · 27/1,180,028 alleles
Filtering AF
0.00157%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00134%
Overall
0.00174%
28/1,612,918 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00229% | 43,705 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,480 |
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.Gly466=
- Coding
- c.1398G>A
- MANE Select
- NM_000063
- Type
- single nucleotide variant
- Location
- chr6:31943262 (GRCh38)
- Gene constraint
- LOEUF 0.909 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.61 · 14 PDB
- Residue 466
- a disulfide bond; the peptidase s1 domain
Similar variants
- 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
- C2 p.Arg176Cys 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-gly466 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown