HCN2 p.Pro71=
c.213G>T · VCV4939401
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.52%, afr)
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 1 | GERP -1.1, phastCons 1 |
| Overall | ||
| CADD | 9.631 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.52%
African / African-American · 845/55,524 alleles
Filtering AF
1.44%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.4%
Overall
0.0936%
913/975,020 alleles · low-frequency
exomes 268/832,532 · genomes 645/142,488 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.52% | 66 |
| Admixed American | 0.122% | 821 |
| Remaining individualsnot grpmax-eligible | 0.099% | 1,010 |
| Finnishnot grpmax-eligible | 0.0121% | 8,234 |
| South Asian | 0.00456% | 21,940 |
| European (non-Finnish) | 0.00218% | 45,814 |
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.Pro71=
- Coding
- c.213G>T
- MANE Select
- NM_001194
- Type
- single nucleotide variant
- Location
- chr19:590158 (GRCh38)
- Gene constraint
- LOEUF 0.627 · pLI 0.18 (gnomAD)
- Structure
- AlphaFold pLDDT 72.28 · 3 PDB
- Residue 71
- the 'disordered' region
Similar variants
- HCN2 p.Pro71Ser Uncertain significance ★ ⚠ same residue
- 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
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-pro71 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown