C6 p.Thr392=
c.1176C>T · rs199976299 · VCV1643335
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00839%, 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 -1.4 | GERP -2.6 |
| Overall | ||
| CADD | 2.998 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00839%
European (non-Finnish) · 99/1,179,668 alleles
Filtering AF
0.00702%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00652%
Overall
0.00651%
105/1,613,370 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00839% | 11,916 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,228 |
| Finnishnot grpmax-eligible | 0.00313% | 31,987 |
| Admixed American | 0.00167% | 59,916 |
| South Asian | 0.0011% | 91,048 |
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
- C6
- Protein
- p.Thr392=
- Coding
- c.1176C>T
- MANE Select
- NM_000065
- dbSNP
- rs199976299
- Type
- single nucleotide variant
- Location
- chr5:41172340 (GRCh38)
- Gene constraint
- LOEUF 1.008 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.72 · 11 PDB
- Residue 392
- the macpf domain
Similar variants
- C6 p.Arg596Ter Pathogenic/Likely pathogenic ★★ same type
- C6 p.Arg606Ter Pathogenic ★★ same type
- C6 p.Cys218Ter Pathogenic/Likely pathogenic ★★ same type
- C6 p.Tyr683Ter Pathogenic/Likely pathogenic ★★ same type
- C6 p.Ala21Val Uncertain significance ★★ ⚠ same type
- C6 p.Ala396Gly Uncertain significance ★★ ⚠ same type
- C6 p.Ala456Thr Uncertain significance ★★ ⚠ same type
- C6 p.Ala500Ser 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/c6-p-thr392 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown