KANK4 p.Ser554=
c.1662G>A · VCV4892518
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0033%, sas)
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 -13 | GERP -4.2 |
| Overall | ||
| CADD | 0.053 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0033%
South Asian · 3/90,928 alleles
Filtering AF
0.000876%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000539%
Overall
0.00118%
19/1,613,536 alleles · very rare
exomes 16/1,461,354 · genomes 3/152,182 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0033% | 30,309 |
| African / African-American | 0.00267% | 37,467 |
| European (non-Finnish) | 0.00119% | 84,274 |
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.Ser554=
- Coding
- c.1662G>A
- MANE Select
- NM_181712
- Type
- single nucleotide variant
- Location
- chr1:62273442 (GRCh38)
- Gene constraint
- LOEUF 0.829 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 57.17
- Residue 554
- 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-ser554 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown