HCN4 p.Val1007=
c.3021G>C · rs1461880931 · VCV1625687
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000432%, nfe)
Conditions
2
Cardiovascular phenotype
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 0.66 | GERP -0.42, phastCons 0.001 |
| Overall | ||
| CADD | 2.882 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000432%
European (non-Finnish) · 5/1,156,906 alleles
Filtering AF
0.000127%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9.2e-05%
Overall
0.000321%
5/1,558,984 alleles · very rare
exomes 3/1,406,874 · genomes 2/152,110 · joint denominator
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
- HCN4
- Protein
- p.Val1007=
- Coding
- c.3021G>C
- MANE Select
- NM_005477
- dbSNP
- rs1461880931
- Type
- single nucleotide variant
- Location
- chr15:73323072 (GRCh38)
- Gene constraint
- LOEUF 0.571 · pLI 0.15 (gnomAD)
- Structure
- AlphaFold pLDDT 61.86 · 8 PDB
- Residue 1007
- the 'disordered' region
Similar variants
- HCN4 p.Val1007Met Uncertain significance ★★ ⚠ same residue
- HCN4 p.Val1007Ala 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
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-val1007 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown