Is PANK2 p.Arg3= (c.7A>C) pathogenic?

PANK2 p.Arg3= (c.7A>C) is classified Likely benign in PANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-22). Very rare (popmax 0.00411%, afr); Associated with pantothenate kinase-associated neurodegeneration.

What condition is associated with PANK2 p.Arg3= (c.7A>C)?

PANK2 p.Arg3= (c.7A>C) is associated with pantothenate kinase-associated neurodegeneration (ClinVar).

How common is PANK2 p.Arg3= (c.7A>C) in the general population?

PANK2 p.Arg3= (c.7A>C) is very rare (popmax 0.00411%, afr) (gnomAD).

PANK2 p.Arg3=

Q: How is Pantothenate kinase-associated neurodegeneration inherited?

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

c.7A>C · rs2515419147 · VCV2866828

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00411%, afr)

Conditions

pantothenate kinase-associated neurodegeneration

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 0.22	GERP -3.1, phastCons 0.033
Overall
CADD	8.137	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00411% African / African-American · 3/72,962 alleles

Filtering AF 0.00109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000503%

Overall 0.000259% 4/1,543,838 alleles · very rare exomes 4/1,391,728 · genomes 0/152,110 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00411%	24,321
European (non-Finnish)	8.75e-05%	1,142,754

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.Arg3=
Coding: c.7A>C
MANE Select: NM_001386393 · reported on NM_153638
dbSNP: rs2515419147
Type: single nucleotide variant
Location: chr20:3889107 (GRCh38)
Gene constraint: LOEUF 1.115 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.99 · 1 PDB

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.Arg3Ser 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-arg3 (accessed [today's date]).

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