C7 p.Thr539=
c.1617G>A · rs368610795 · VCV1574883
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0362%, afr)
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 -5.6 | GERP -5.5 |
| Overall | ||
| CADD | 0.05 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0362%
African / African-American · 27/74,638 alleles
Filtering AF
0.0255%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.022%
Overall
0.0144%
231/1,608,456 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0362% | 2,764 |
| European (non-Finnish) | 0.016% | 6,267 |
| South Asian | 0.0155% | 6,447 |
| Remaining individualsnot grpmax-eligible | 0.00322% | 31,055 |
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.Thr539=
- Coding
- c.1617G>A
- MANE Select
- NM_001565 · reported on NM_000587
- dbSNP
- rs368610795
- Type
- single nucleotide variant
- Location
- chr5:40959576 (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-thr539 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown