KCNN2 p.Pro199=
c.597C>G · VCV4821874
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0173%, mid)
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 3.4 | GERP 2.7, phastCons 1 |
| Overall | ||
| CADD | 14.38 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0173%
Middle Eastern · 1/5,776 alleles
Filtering AF
0.000784%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000622%
Overall
0.00124%
19/1,535,716 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0173% | 5,776 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00394% | 25,412 |
| Remaining individualsnot grpmax-eligible | 0.00168% | 59,434 |
| European (non-Finnish) | 0.00131% | 76,570 |
| South Asian | 0.00126% | 79,600 |
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
- KCNN2
- Protein
- p.Pro199=
- Coding
- c.597C>G
- MANE Select
- NM_021614
- Type
- single nucleotide variant
- Location
- chr5:114362736 (GRCh38)
- Gene constraint
- LOEUF 0.661 · pLI 0.07 (gnomAD)
- Structure
- AlphaFold pLDDT 77.98 · 16 PDB
- Residue 199
- a UniProt-annotated variant site (in nedmab)
Similar variants
- KCNN2 p.Gly574Ser Pathogenic ★★ same type
- KCNN2 p.Tyr573Cys Pathogenic/Likely pathogenic ★★ same type
- KCNN2 p.Arg233Leu Uncertain significance ★★ ⚠ same type
- KCNN2 p.Asn412Ser Uncertain significance ★★ ⚠ same type
- KCNN2 p.Gln15Ter Uncertain significance ★★ same type
- KCNN2 p.Ile730Val Uncertain significance ★★ ⚠ same type
- KCNN2 p.Ile744Met Uncertain significance ★★ ⚠ same type
- KCNN2 p.Lys332Arg 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/kcnn2-p-pro199 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown