Is PANK2 p.Ala15= (c.45G>A) pathogenic?

PANK2 p.Ala15= (c.45G>A) is classified Likely benign in PANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-25). Very rare (popmax 0.000345%, nfe); Associated with pantothenate kinase-associated neurodegeneration.

What condition is associated with PANK2 p.Ala15= (c.45G>A)?

PANK2 p.Ala15= (c.45G>A) is associated with pantothenate kinase-associated neurodegeneration (ClinVar).

How common is PANK2 p.Ala15= (c.45G>A) in the general population?

PANK2 p.Ala15= (c.45G>A) is very rare (popmax 0.000345%, nfe) (gnomAD).

PANK2 p.Ala15=

Q: How is Pantothenate kinase-associated neurodegeneration inherited?

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

c.45G>A · rs764726817 · VCV2910876

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000345%, nfe)

Conditions

pantothenate kinase-associated neurodegeneration

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.86	GERP 1.8, phastCons 0.059
Overall
CADD	18.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000345% European (non-Finnish) · 4/1,160,382 alleles

Filtering AF 8.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000254% 4/1,575,864 alleles · very rare exomes 4/1,423,538 · genomes 0/152,326 · 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.Ala15=
Coding: c.45G>A
MANE Select: NM_001386393 · reported on NM_153638
dbSNP: rs764726817
Type: single nucleotide variant
Location: chr20:3889145 (GRCh38)

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)

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-ala15 (accessed [today's date]).

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