KANK4 p.Ser109=
c.327A>G · rs2666507 · VCV1182584
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 83.4%, eas) — too common for a highly-penetrant pathogenic allele
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 -6.4 | GERP -4.2 |
| Overall | ||
| CADD | 0.058 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
83.4%
East Asian · 37,350/44,788 alleles
Filtering AF
82.7%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 82.4%
Overall
70.1%
1,130,248/1,613,228 alleles · common
exomes 1,019,290/1,461,666 · genomes 110,958/151,562 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 83.4% | 1 |
| Finnishnot grpmax-eligible | 80.9% | 1 |
| Admixed American | 80.8% | 1 |
| African / African-American | 77.7% | 1 |
| South Asian | 74.1% | 1 |
| Remaining individualsnot grpmax-eligible | 70.4% | 1 |
| European (non-Finnish) | 67.8% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 64.4% | 2 |
| Middle Eastern | 63.9% | 2 |
| Amishnot grpmax-eligible | 60.5% | 2 |
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.Ser109=
- Coding
- c.327A>G
- MANE Select
- NM_181712
- dbSNP
- rs2666507
- Type
- single nucleotide variant
- Location
- chr1:62274777 (GRCh38)
- Gene constraint
- LOEUF 0.829 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 57.17
- Residue 109
- the 'disordered' region
Similar variants
- 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
- KANK4 p.Asp266Gly Uncertain significance ★★ ⚠ same type
- KANK4 p.Asp459Val 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-ser109 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown