C6 p.Gln274=
c.822G>A · rs150318194 · VCV2112472
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00401%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.6 | GERP -3.6 |
| Overall | ||
| CADD | 0.024 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00401%
African / African-American · 3/74,900 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000495%
Overall
0.000496%
8/1,613,676 alleles · very rare
exomes 6/1,461,510 · genomes 2/152,166 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00401% | 24,967 |
| European (non-Finnish) | 0.000424% | 235,963 |
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.Gln274=
- Coding
- c.822G>A
- MANE Select
- NM_000065
- dbSNP
- rs150318194
- Type
- single nucleotide variant
- Location
- chr5:41181464 (GRCh38)
- Gene constraint
- LOEUF 1.008 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.72 · 11 PDB
- Residue 274
- the macpf domain
Similar variants
- C6 p.Gln274Arg Uncertain significance ★★ ⚠ same residue
- C6 p.Gln274His Uncertain significance ★ ⚠ same residue
- C6 p.Gln274Lys Uncertain significance ★ ⚠ same residue
- C6 p.Gln274fs Pathogenic/Likely pathogenic ★★ same residue
- 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
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-gln274 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown