KANK2 p.Pro321=
c.963G>C · rs199627538 · VCV2040838
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0101%, amr)
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 -12 | GERP -12 |
| Overall | ||
| CADD | 0.022 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0101%
Admixed American · 6/59,556 alleles
Filtering AF
0.00431%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00297%
Overall
0.000934%
15/1,605,410 alleles · ultra-rare
exomes 13/1,453,220 · genomes 2/152,190 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0101% | 9,926 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 61,986 |
| European (non-Finnish) | 0.00068% | 146,957 |
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
- KANK2
- Protein
- p.Pro321=
- Coding
- c.963G>C
- MANE Select
- NM_001136191
- dbSNP
- rs199627538
- Type
- single nucleotide variant
- Location
- chr19:11193117 (GRCh38)
- Gene constraint
- LOEUF 0.704 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.58 · 3 PDB
- Residue 321
- the 'disordered' region
Similar variants
- KANK2 p.Pro321Ser Uncertain significance ★★ ⚠ same residue
- KANK2 p.Ala182Val Uncertain significance ★★ ⚠ same type
- KANK2 p.Ala317Val Uncertain significance ★★ ⚠ same type
- KANK2 p.Ala347Thr Uncertain significance ★★ ⚠ same type
- KANK2 p.Ala351Thr Uncertain significance ★★ ⚠ same type
- KANK2 p.Ala393Gly Uncertain significance ★★ ⚠ same type
- KANK2 p.Ala653Val Uncertain significance ★★ ⚠ same type
- KANK2 p.Ala711Val 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/kank2-p-pro321 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown