HCN1 p.Pro87=
c.261C>G · rs199612501 · VCV530592
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.312%, sas)
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 2.3 | GERP -3.3, phastCons 1 |
| Overall | ||
| CADD | 11.62 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.312%
South Asian · 283/90,700 alleles
Filtering AF
0.282%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.27%
Overall
0.0195%
313/1,604,048 alleles · rare
exomes 294/1,452,310 · genomes 19/151,738 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.312% | 320 |
| Middle Eastern | 0.0499% | 2,004 |
| Remaining individualsnot grpmax-eligible | 0.0129% | 7,782 |
| East Asian | 0.00225% | 44,416 |
| European (non-Finnish) | 0.00144% | 69,304 |
| African / African-American | 0.00134% | 74,430 |
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.Pro87=
- Coding
- c.261C>G
- MANE Select
- NM_021072
- dbSNP
- rs199612501
- Type
- single nucleotide variant
- Location
- chr5:45695833 (GRCh38)
- Gene constraint
- LOEUF 0.329 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 70.61 · 17 PDB
- Residue 87
- the 'disordered' region
Similar variants
- HCN1 p.Pro87Ser Benign/Likely benign ★★ same residue
- HCN1 p.Pro87Arg Uncertain significance ★ ⚠ 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
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-pro87 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown