Is PANK2 p.Glu129= (c.387G>A) pathogenic?

PANK2 p.Glu129= (c.387G>A) is classified Likely benign in PANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-16). Very rare (popmax 8.47e-05%, nfe); Associated with pantothenate kinase-associated neurodegeneration.

What condition is associated with PANK2 p.Glu129= (c.387G>A)?

PANK2 p.Glu129= (c.387G>A) is associated with pantothenate kinase-associated neurodegeneration (ClinVar).

How common is PANK2 p.Glu129= (c.387G>A) in the general population?

PANK2 p.Glu129= (c.387G>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

PANK2 p.Glu129=

Q: How is Pantothenate kinase-associated neurodegeneration inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.387G>A · rs748467775 · VCV2867043

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

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 2.9	GERP -1.8, phastCons 1
Overall
CADD	7.254	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,034 alleles

Overall 6.2e-05% 1/1,614,146 alleles · very rare exomes 1/1,461,886 · genomes 0/152,260 · joint denominator

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.Glu129=
Coding: c.387G>A
MANE Select: NM_001386393
dbSNP: rs748467775
Type: single nucleotide variant
Location: chr20:3908014 (GRCh38)
Gene constraint: LOEUF 1.115 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.99 · 1 PDB
Residue 129: the 'disordered' region

Full PANK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pantothenate kinase-associated neurodegeneration — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Pantothenate kinase-associated neurodegeneration (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

PANK2 p.Glu129Asp Uncertain significance ★ ⚠ same residue
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

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-glu129 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown