HCN4 p.Pro16=
c.48G>T · rs376849038 · VCV2118446
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Not reported
no allele count reported in gnomAD v4.1 (AN 1,527,124)
Conditions
1
Brugada syndrome 8
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 3.5 | GERP 0.85, phastCons 1 |
| Overall | ||
| CADD | 14.52 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
No allele count reported in gnomAD v4.1 (AN 1,527,124). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.
Variant & gene context
- Gene
- HCN4
- Protein
- p.Pro16=
- Coding
- c.48G>T
- MANE Select
- NM_005477
- dbSNP
- rs376849038
- Type
- single nucleotide variant
- Location
- chr15:73368223 (GRCh38)
- Gene constraint
- LOEUF 0.571 · pLI 0.15 (gnomAD)
- Structure
- AlphaFold pLDDT 61.86 · 8 PDB
- Residue 16
- the 'disordered' region
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.Pro16Leu 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-pro16 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown