PANK2 p.Ser21=
c.63T>C · VCV4944250
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00172%, amr)
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 -0.27 | GERP -3.4 |
| Overall | ||
| CADD | 7.05 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00172%
Admixed American · 1/58,246 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000312%
5/1,600,426 alleles · very rare
exomes 5/1,448,132 · genomes 0/152,294 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00172% | 58,246 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 61,940 |
| European (non-Finnish) | 0.000256% | 391,209 |
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
- PANK2
- Protein
- p.Ser21=
- Coding
- c.63T>C
- MANE Select
- NM_001386393 · reported on NM_153638
- Type
- single nucleotide variant
- Location
- chr20:3889163 (GRCh38)
- Gene constraint
- LOEUF 1.115 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.99 · 1 PDB
Similar variants
- PANK2 p.Ser21Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
- PANK2 c.1082+1G>C Likely pathogenic ★★ same type
- PANK2 c.1083-1G>T Pathogenic/Likely pathogenic ★★ same type
- PANK2 c.1207-3C>G Pathogenic/Likely pathogenic ★★ same type
- PANK2 c.299-1G>A Likely pathogenic ★★ same type
- PANK2 c.905+1G>C Pathogenic ★★ same type
- PANK2 c.-21G>T Pathogenic/Likely pathogenic ★★ same type
- PANK2 p.Arg154Gln Pathogenic/Likely pathogenic ★★ 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/pank2-p-ser21 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown