HCN2 p.Asp381=
c.1143C>T · rs202076978 · VCV739876
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.689%, eas)
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 -6.8 | GERP -4 |
| Overall | ||
| CADD | 7.22 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.689%
East Asian · 309/44,876 alleles
Filtering AF
0.625%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.601%
Overall
0.0305%
492/1,611,752 alleles · rare
exomes 443/1,459,594 · genomes 49/152,158 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.689% | 145 |
| South Asian | 0.0384% | 2,601 |
| Remaining individualsnot grpmax-eligible | 0.0321% | 3,118 |
| Admixed American | 0.015% | 6,665 |
| European (non-Finnish) | 0.00992% | 10,082 |
| African / African-American | 0.00267% | 37,462 |
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
- HCN2
- Protein
- p.Asp381=
- Coding
- c.1143C>T
- MANE Select
- NM_001194
- dbSNP
- rs202076978
- Type
- single nucleotide variant
- Location
- chr19:605147 (GRCh38)
- Gene constraint
- LOEUF 0.627 · pLI 0.18 (gnomAD)
- Structure
- AlphaFold pLDDT 72.28 · 3 PDB
Similar variants
- HCN2 p.Met374Leu Pathogenic/Likely pathogenic ★★ same type
- HCN2 p.Arg264Cys Uncertain significance ★★ ⚠ same type
- HCN2 p.Arg396His Uncertain significance ★★ ⚠ same type
- HCN2 p.Arg474Cys Uncertain significance ★★ ⚠ same type
- HCN2 p.Asp502Asn Uncertain significance ★★ ⚠ same type
- HCN2 p.Asp625Asn Uncertain significance ★★ same type
- HCN2 p.Glu148Val Uncertain significance ★★ ⚠ same type
- HCN2 p.Gly712Asp Uncertain significance ★★ ⚠ same type
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/hcn2-p-asp381 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown