KCNH2 p.Pro2=
c.6G>C · VCV3862765
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00017%, nfe)
Conditions
1
Cardiovascular phenotype
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 -0.11 | GERP -3.6, phastCons 0.44 |
| Overall | ||
| CADD | 12.53 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00017%
European (non-Finnish) · 2/1,176,800 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000125%
2/1,604,498 alleles · very rare
exomes 2/1,453,802 · genomes 0/150,696 · 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
- KCNH2
- Protein
- p.Pro2=
- Coding
- c.6G>C
- MANE Select
- NM_000238
- Type
- single nucleotide variant
- Location
- chr7:150977908 (GRCh38)
- Gene constraint
- LOEUF 0.568 · pLI 0.07 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 63.94 · 24 PDB
Similar variants
- KCNH2 p.Pro2Ser Uncertain significance ★ ⚠ same residue
- KCNH2 p.Pro2Leu Uncertain significance ★ ⚠ same residue
- KCNH2 c.1557+1G>C Pathogenic/Likely pathogenic ★★ same condition
- KCNH2 c.1945+6T>C Pathogenic/Likely pathogenic ★★ same condition
- KCNH2 c.1946-2A>C Pathogenic ★★ same condition
- KCNH2 c.2145+1G>A Pathogenic/Likely pathogenic ★★ same condition
- KCNH2 c.2592+1G>A Pathogenic/Likely pathogenic ★★ same condition
- KCNH2 p.Ala490Thr Pathogenic/Likely pathogenic ★★ 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/kcnh2-p-pro2 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown