C7 p.Arg458=
c.1374G>A · rs571005172 · VCV1652611
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00669%, eas)
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 0.57 | GERP -1.4, phastCons 0.033 |
| Overall | ||
| CADD | 4.226 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00669%
East Asian · 3/44,876 alleles
Filtering AF
0.00177%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.00031%
5/1,613,846 alleles · very rare
exomes 3/1,461,576 · genomes 2/152,270 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00669% | 14,959 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,239 |
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.Arg458=
- Coding
- c.1374G>A
- MANE Select
- NM_000587
- dbSNP
- rs571005172
- Type
- single nucleotide variant
- Location
- chr5:40958146 (GRCh38)
- Structure
- AlphaFold pLDDT 89.67 · 6 PDB
Similar variants
- C7 p.Arg458Trp Uncertain significance ★★ ⚠ same residue
- C7 p.Arg458Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
- 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
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-arg458 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown