PANK2 p.Phe253=
c.759T>C · rs2515499760 · VCV2852230
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
pantothenate kinase-associated neurodegeneration
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 1.2 | GERP 0.75, phastCons 1 |
| Overall | ||
| CADD | 8.991 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- PANK2
- Protein
- p.Phe253=
- Coding
- c.759T>C
- MANE Select
- NM_001386393
- dbSNP
- rs2515499760
- Type
- single nucleotide variant
- Location
- chr20:3910684 (GRCh38)
- Gene constraint
- LOEUF 1.115 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.99 · 1 PDB
- Residue 253
- an α-helix
Disease context
pantothenate kinase-associated neurodegeneration — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Pantothenate kinase-associated neurodegeneration (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- All ages
- Prevalence
- 1-9 / 1 000 000 (Europe)
Similar variants
- PANK2 c.1082+1G>C Likely pathogenic ★★ same condition
- PANK2 c.1083-1G>T Pathogenic/Likely pathogenic ★★ same condition
- PANK2 c.1207-3C>G Pathogenic/Likely pathogenic ★★ same condition
- PANK2 c.299-1G>A Likely pathogenic ★★ same condition
- PANK2 c.905+1G>C Pathogenic ★★ same condition
- PANK2 c.-21G>T Pathogenic/Likely pathogenic ★★ same condition
- PANK2 p.Arg154Gln Pathogenic/Likely pathogenic ★★ same condition
- PANK2 p.Arg154Trp Pathogenic/Likely pathogenic ★★ same condition
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-phe253 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown