KCND3 p.Phe351=
c.1053C>T · rs758371576 · VCV2729842
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000169%, nfe)
Conditions
2
Cardiovascular phenotype
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 7.6 | GERP 1.1, phastCons 1 |
| Overall | ||
| CADD | 8.662 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000169%
European (non-Finnish) · 2/1,180,044 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000124%
2/1,614,056 alleles · very rare
exomes 1/1,461,888 · genomes 1/152,168 · 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
- KCND3
- Protein
- p.Phe351=
- Coding
- c.1053C>T
- MANE Select
- NM_001378969
- dbSNP
- rs758371576
- Type
- single nucleotide variant
- Location
- chr1:111981674 (GRCh38)
- Gene constraint
- LOEUF 0.303 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 71.32 · 6 PDB
Similar variants
- KCND3 p.Phe351Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- 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
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-phe351 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown