KANK4 p.Pro286=
c.858G>A · rs368045332 · VCV1596224
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, 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 -0.74 | GERP -3.7, phastCons 0.001 |
| Overall | ||
| CADD | 7.574 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.00723%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0055%
Overall
0.00527%
85/1,613,706 alleles · ultra-rare
exomes 76/1,461,572 · genomes 9/152,134 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| African / African-American | 0.0134% | 7,490 |
| European (non-Finnish) | 0.00568% | 17,610 |
| South Asian | 0.00439% | 22,758 |
| East Asian | 0.00223% | 44,866 |
| Admixed American | 0.00167% | 59,964 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,478 |
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
- KANK4
- Protein
- p.Pro286=
- Coding
- c.858G>A
- MANE Select
- NM_181712
- dbSNP
- rs368045332
- Type
- single nucleotide variant
- Location
- chr1:62274246 (GRCh38)
- Gene constraint
- LOEUF 0.829 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 57.17
Similar variants
- KANK4 p.Pro286Leu Benign/Likely benign ★★ same residue
- KANK4 p.Pro286Ser Uncertain significance ★ ⚠ same residue
- KANK4 p.Ala115Val Uncertain significance ★★ ⚠ same type
- KANK4 p.Ala987Thr Uncertain significance ★★ ⚠ same type
- KANK4 p.Arg336Met Uncertain significance ★★ ⚠ same type
- KANK4 p.Arg471Cys Uncertain significance ★★ ⚠ same type
- KANK4 p.Arg653Cys Uncertain significance ★★ ⚠ same type
- KANK4 p.Arg790Gln 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/kank4-p-pro286 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown