KCNN3 p.Pro515=
c.1545C>A · rs557553959 · VCV3025444
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.085%, amr)
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 1.1 | GERP -3.9, phastCons 1 |
| Overall | ||
| CADD | 5.964 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.085%
Admixed American · 51/60,024 alleles
Filtering AF
0.0663%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0598%
Overall
0.00489%
79/1,614,114 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.085% | 1,177 |
| Remaining individualsnot grpmax-eligible | 0.0192% | 5,209 |
| African / African-American | 0.00133% | 75,026 |
| European (non-Finnish) | 0.00127% | 78,666 |
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
- KCNN3
- Protein
- p.Pro515=
- Coding
- c.1545C>A
- MANE Select
- NM_002249
- dbSNP
- rs557553959
- Type
- single nucleotide variant
- Location
- chr1:154733048 (GRCh38)
- Gene constraint
- LOEUF 0.379 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 68.54
Similar variants
- KCNN3 p.Ala536Thr Pathogenic/Likely pathogenic ★★ same type
- KCNN3 p.Arg224Gln Uncertain significance ★★ ⚠ same type
- KCNN3 p.Glu204Gly Uncertain significance ★★ ⚠ same type
- KCNN3 p.Val716Phe Uncertain significance ★★ ⚠ same type
- KCNN3 c.1702-3T>C Likely benign ★★ same type
- KCNN3 p.Ala229= Likely benign ★★ same type
- KCNN3 p.Asn349= Benign ★★ same type
- KCNN3 p.Glu381Gln Likely benign ★★ 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/kcnn3-p-pro515 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown