KANK4 p.Pro625=
c.1875G>T · VCV4692167
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0083%, nfe)
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 -20 | GERP -4.2 |
| Overall | ||
| CADD | 0.005 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0083%
European (non-Finnish) · 94/1,132,734 alleles
Filtering AF
0.00692%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00642%
Overall
0.00639%
97/1,516,836 alleles · very rare
exomes 90/1,364,672 · genomes 7/152,164 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0083% | 12,050 |
| Remaining individualsnot grpmax-eligible | 0.00344% | 29,067 |
| African / African-American | 0.00139% | 71,820 |
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.Pro625=
- Coding
- c.1875G>T
- MANE Select
- NM_181712
- Type
- single nucleotide variant
- Location
- chr1:62273229 (GRCh38)
- Gene constraint
- LOEUF 0.829 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 57.17
- Residue 625
- the 'disordered' region
Similar variants
- KANK4 p.Pro625Leu 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
- KANK4 p.Asp266Gly 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-pro625 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown