HCN1 p.Pro7=
c.21C>G · rs1339322889 · VCV2742192
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00755%, eas)
Conditions
1
early-infantile DEE
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 3.7 | GERP -0.3, phastCons 1 |
| Overall | ||
| CADD | 13.46 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00755%
East Asian · 2/26,474 alleles
Filtering AF
0.00125%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000467%
Overall
0.000148%
2/1,353,242 alleles · very rare
exomes 0/1,203,830 · genomes 2/149,412 · 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
- HCN1
- Protein
- p.Pro7=
- Coding
- c.21C>G
- MANE Select
- NM_021072
- dbSNP
- rs1339322889
- Type
- single nucleotide variant
- Location
- chr5:45696073 (GRCh38)
- Gene constraint
- LOEUF 0.329 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 70.61 · 17 PDB
- Residue 7
- the 'disordered' region
Similar variants
- HCN1 p.Pro7Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
- HCN1 p.Gly391Ser Pathogenic ★★ same condition
- HCN1 p.His279Tyr Pathogenic/Likely pathogenic ★★ same condition
- HCN1 p.Ser100Phe Pathogenic/Likely pathogenic ★★ same condition
- HCN1 c.1230+1G>T Uncertain significance ★★ same condition
- HCN1 p.Ala479Thr Uncertain significance ★★ ⚠ same condition
- HCN1 p.Ala507Thr Uncertain significance ★★ ⚠ same condition
- HCN1 p.Ala670Glu Uncertain significance ★★ 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/hcn1-p-pro7 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown