Is PANK2 p.Arg44fs (c.126del) pathogenic?

PANK2 p.Arg44fs (c.126del) is classified Uncertain significance in PANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-12). Very rare (popmax 0.00334%, amr); Associated with pantothenate kinase-associated neurodegeneration.

What condition is associated with PANK2 p.Arg44fs (c.126del)?

PANK2 p.Arg44fs (c.126del) is associated with pantothenate kinase-associated neurodegeneration (ClinVar).

How common is PANK2 p.Arg44fs (c.126del) in the general population?

PANK2 p.Arg44fs (c.126del) is very rare (popmax 0.00334%, amr) (gnomAD).

PANK2 p.Arg44fs

Q: How is Pantothenate kinase-associated neurodegeneration inherited?

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

c.126del · rs1600474748 · VCV642965

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Conditions

pantothenate kinase-associated neurodegeneration

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.04	GERP 1.7

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,942 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,613,142 alleles · very rare exomes 2/1,460,768 · genomes 0/152,374 · 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.Arg44fs
Coding: c.126del
MANE Select: NM_001386393 · reported on NM_153638
dbSNP: rs1600474748
Type: Deletion
Location: chr20:3889226 (GRCh38)
Gene constraint: LOEUF 1.115 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.99 · 1 PDB
Residue 44: 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.Arg44Leu Uncertain significance ★★ ⚠ same residue
PANK2 p.Arg371_Glu372delinsGln Pathogenic/Likely pathogenic ★★ same condition
PANK2 p.Gly363_Asn364insTer Pathogenic ★★ same condition
PANK2 p.Gly451fs Pathogenic/Likely pathogenic ★★ same condition
PANK2 p.Ser59fs Pathogenic/Likely pathogenic ★★ same condition
PANK2 p.Ser81fs Pathogenic ★★ same condition
PANK2 p.Tyr252fs Pathogenic/Likely pathogenic ★★ same condition
PANK2 c.906-21_906-19del Likely benign ★★ 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-arg44fs (accessed [today's date]).

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