Sugi Variant

Sugi Variant/HCN1

HCN1 — 1094 ClinVar variants

All ClinVar germline HCN1 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 496 flagged for review →

19 Pathogenic · 2 Pathogenic/Likely pathogenic · 21 Likely pathogenic · 52 Conflicting · 18 Benign · 18 Benign/Likely benign · 386 Likely benign · 578 Uncertain significance

Full HCN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 496

Variants where the independent computational evidence doesn't line up with the clinical picture — a QC signal for a second look, not a reclassification.

Predictors vs ClinVar 1

ClinVar calls these pathogenic, but the computational predictors lean tolerated — the highest-value review flag.

Predictors agree, ClinVar conflicts 33

ClinVar submitters conflict, but the independent predictors unanimously agree — a QC review flag, not a reclassification.

Predicted LoF vs a conflicting call 1

ClinVar submitters conflict, and it's a predicted loss-of-function change in a gene where LoF causes disease — flagged for review, not resolved (verify NMD-escape for C-terminal truncations). Non-missense.

Predictors lean, ClinVar uncertain 391

ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification. · showing the 150 best-reviewed of 391

Predictors split 70

The independent predictors disagree with each other — read with care.

All HCN1 variants

Pathogenic 19

  • p.Gly391Ser Multiple submitters developmental and epileptic encephalopathy, 24
  • p.Ser272Pro Multiple submitters developmental and epileptic encephalopathy, 24
  • p.Ala387Gly Single submitter early-infantile DEE
  • p.Arg195Ser Single submitter early-infantile DEE
  • p.Arg297Thr Single submitter early-infantile DEE
  • p.Gly391Cys Single submitter developmental and epileptic encephalopathy, 24
  • p.Gly391Val Single submitter early-infantile DEE
  • p.Gly521Val Single submitter developmental and epileptic encephalopathy, 24 ⚠
  • p.Ile380Phe Single submitter early-infantile DEE
  • p.Ser264Cys Single submitter early-infantile DEE
  • p.Tyr234Phe Single submitter early-infantile DEE
  • p.Ala395Gly No assertion criteria generalized epilepsy with febrile seizures plus, type 10
  • p.Arg590Gln No assertion criteria generalized epilepsy with febrile seizures plus, type 10
  • p.Cys329Ser No assertion criteria generalized epilepsy with febrile seizures plus, type 10 ⚠
  • p.Glu246Ala No assertion criteria Febrile seizure (within the age range of 3 months to 6 years)
  • p.Leu157Val No assertion criteria generalized epilepsy with febrile seizures plus, type 10
  • p.Met243Arg No assertion criteria generalized epilepsy with febrile seizures plus, type 10
  • p.Val390Ala No assertion criteria generalized epilepsy with febrile seizures plus, type 10
  • p.Val414Met No assertion criteria generalized epilepsy with febrile seizures plus, type 10

Pathogenic/Likely pathogenic 2

Likely pathogenic 21

  • p.Gly391Asp Multiple submitters developmental and epileptic encephalopathy, 24
  • p.Leu265His Multiple submitters developmental and epileptic encephalopathy, 24
  • p.Ala294Val Single submitter early-infantile DEE
  • p.Ala383Val Single submitter
  • p.Ala387Pro Single submitter early-infantile DEE
  • p.Ala387Thr Single submitter early-infantile DEE
  • p.Asn179Tyr Single submitter developmental and epileptic encephalopathy, 24
  • p.Gly303Val Single submitter early-infantile DEE
  • p.Gly382Arg Single submitter
  • p.His286Gln Single submitter
  • p.Ile397Met Single submitter
  • p.Met153Ile Single submitter Inborn genetic diseases ⚠
  • p.Met305Leu Single submitter developmental and epileptic encephalopathy, 24
  • p.Met376Arg Single submitter HCN1-related disorder
  • p.Met379Arg Single submitter generalized epilepsy with febrile seizures plus, type 10
  • p.Phe167Leu Single submitter generalized epilepsy with febrile seizures plus, type 10 ⚠
  • p.Pro137_Tyr138insTer Single submitter developmental and epileptic encephalopathy, 24
  • p.Pro210Ser Single submitter generalized epilepsy with febrile seizures plus, type 10
  • p.Thr260Ile Single submitter
  • p.Pro366Thr No assertion criteria developmental and epileptic encephalopathy, 24
  • p.Ser710fs No assertion criteria generalized epilepsy with febrile seizures plus, type 10

Conflicting classifications of pathogenicity 52

Benign 18

Benign/Likely benign 18

  • c.1012-14A>G Multiple submitters early-infantile DEE
  • c.1783+4C>T Multiple submitters Inborn genetic diseases
  • p.Ala479= Multiple submitters Inborn genetic diseases
  • p.Ala724= Multiple submitters early-infantile DEE
  • p.Asn570= Multiple submitters Inborn genetic diseases
  • p.Cys542= Multiple submitters early-infantile DEE
  • p.Gly382= Multiple submitters early-infantile DEE
  • p.Gly47Val Multiple submitters early-infantile DEE
  • p.Gly72_Gly74del Multiple submitters early-infantile DEE
  • p.Gly72_Gly74dup Multiple submitters early-infantile DEE
  • p.Pro42Ser Multiple submitters Inborn genetic diseases
  • p.Pro743Ala Multiple submitters early-infantile DEE
  • p.Pro744Leu Multiple submitters Inborn genetic diseases
  • p.Pro87= Multiple submitters early-infantile DEE
  • p.Pro87Ser Multiple submitters early-infantile DEE
  • p.Ser599= Multiple submitters early-infantile DEE
  • p.Thr655= Multiple submitters early-infantile DEE
  • p.Tyr347= Multiple submitters early-infantile DEE

Likely benign 386

Showing the top 300 by review status; the full set is in the sitemap.

Uncertain significance 578

Showing the top 300 by review status; the full set is in the sitemap.