KCND3 p.Pro217=
c.651G>A · rs186974111 · VCV507820
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0495%, mid)
Conditions
2
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 -9.2 | GERP -4.2 |
| Overall | ||
| CADD | 7.677 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0495%
Middle Eastern · 3/6,062 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0101%
Overall
0.00595%
96/1,613,712 alleles · ultra-rare
exomes 83/1,461,680 · genomes 13/152,032 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0495% | 2,021 |
| Admixed American | 0.0217% | 4,616 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,813 |
| European (non-Finnish) | 0.00602% | 16,619 |
| South Asian | 0.0011% | 91,044 |
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
- KCND3
- Protein
- p.Pro217=
- Coding
- c.651G>A
- MANE Select
- NM_001378969
- dbSNP
- rs186974111
- Type
- single nucleotide variant
- Location
- chr1:111982076 (GRCh38)
- Gene constraint
- LOEUF 0.303 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 71.32 · 6 PDB
Similar variants
- KCND3 p.Arg290Gln Likely pathogenic ★★ same condition
- KCND3 p.Gly384Ser Pathogenic/Likely pathogenic ★★ same condition
- KCND3 p.Pro375Ser Pathogenic/Likely pathogenic ★★ same condition
- KCND3 p.Thr377Met Pathogenic ★★ same condition
- KCND3 p.Val392Ile Pathogenic/Likely pathogenic ★★ same condition
- KCND3 p.Ala144Thr Uncertain significance ★★ ⚠ same condition
- KCND3 p.Ala15Val Uncertain significance ★★ ⚠ same condition
- KCND3 p.Ala172Thr 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/kcnd3-p-pro217 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown