C7 p.Leu491=
c.1473C>T · rs376291154 · VCV1583802
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0166%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.37 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.5 | GERP -4.6 |
| Overall | ||
| CADD | 2.783 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0166%
Middle Eastern · 1/6,040 alleles
Filtering AF
0.0112%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0105%
Overall
0.0103%
166/1,605,004 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0166% | 6,040 |
| European (non-Finnish) | 0.0129% | 7,780 |
| East Asian | 0.0112% | 8,968 |
| African / African-American | 0.00668% | 14,960 |
| Remaining individualsnot grpmax-eligible | 0.00644% | 15,527 |
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
- C7
- Protein
- p.Leu491=
- Coding
- c.1473C>T
- MANE Select
- NM_001565 · reported on NM_000587
- dbSNP
- rs376291154
- Type
- single nucleotide variant
- Location
- chr5:40958245 (GRCh38)
- Structure
- AlphaFold pLDDT 89.67 · 6 PDB
Similar variants
- C7 c.281-1G>T Pathogenic/Likely pathogenic ★★ same type
- C7 c.63-1G>A Pathogenic ★★ same type
- C7 c.739-2A>G Likely pathogenic ★★ same type
- C7 p.Arg402Ter Pathogenic/Likely pathogenic ★★ same type
- C7 p.Gln271Ter Pathogenic/Likely pathogenic ★★ same type
- C7 p.Gly379Arg Pathogenic/Likely pathogenic ★★ same type
- C7 p.Trp205Ter Pathogenic/Likely pathogenic ★★ same type
- C7 p.Ala359Thr 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/c7-p-leu491 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown