HCN4 p.Pro601=
c.1803C>T · VCV3662753
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Brugada syndrome 8
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 0.22 | GERP -1.8, phastCons 0.9 |
| Overall | ||
| CADD | 8.383 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- HCN4
- Protein
- p.Pro601=
- Coding
- c.1803C>T
- MANE Select
- NM_005477
- Type
- single nucleotide variant
- Location
- chr15:73325130 (GRCh38)
- Gene constraint
- LOEUF 0.571 · pLI 0.15 (gnomAD)
- Structure
- AlphaFold pLDDT 61.86 · 8 PDB
- Residue 601
- an α-helix
Disease context
Brugada syndrome 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Brugada syndrome (Orphanet):
- Inheritance
- Autosomal dominant, Not applicable
- Onset
- Adult, Childhood
- Prevalence
- 1-5 / 10 000 (Europe)
Similar variants
- HCN4 p.Pro601Ser Uncertain significance ★ ⚠ same residue
- HCN4 c.2143+1G>A Likely pathogenic ★★ same condition
- HCN4 p.Ala485Val Pathogenic/Likely pathogenic ★★ same condition
- HCN4 p.Arg375Cys Pathogenic/Likely pathogenic ★★ same condition
- HCN4 p.Gly480Ser Pathogenic/Likely pathogenic ★★ same condition
- HCN4 p.Gly480Val Likely pathogenic ★★ same condition
- HCN4 p.Gly482Arg Pathogenic/Likely pathogenic ★★ same condition
- HCN4 p.Tyr354Cys Pathogenic/Likely pathogenic ★★ same condition
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/hcn4-p-pro601 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown