Is PANK2 p.Asp342= (c.1026T>C) pathogenic?

PANK2 p.Asp342= (c.1026T>C) is classified Likely benign in PANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). Very rare (popmax 0.00445%, eas); Associated with pantothenate kinase-associated neurodegeneration.

What condition is associated with PANK2 p.Asp342= (c.1026T>C)?

PANK2 p.Asp342= (c.1026T>C) is associated with pantothenate kinase-associated neurodegeneration (ClinVar).

How common is PANK2 p.Asp342= (c.1026T>C) in the general population?

PANK2 p.Asp342= (c.1026T>C) is very rare (popmax 0.00445%, eas) (gnomAD).

PANK2 p.Asp342=

Q: How is Pantothenate kinase-associated neurodegeneration inherited?

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

c.1026T>C · rs1394589701 · VCV2911097

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00445%, eas)

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 0.6	GERP 0.025, phastCons 1
Overall
CADD	10.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00445% East Asian · 2/44,896 alleles

Filtering AF 0.000738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000248% 4/1,613,966 alleles · very rare exomes 3/1,461,894 · genomes 1/152,072 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00445%	22,448
African / African-American	0.00134%	74,894
European (non-Finnish)	8.47e-05%	1,180,008

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.Asp342=
Coding: c.1026T>C
MANE Select: NM_001386393
dbSNP: rs1394589701
Type: single nucleotide variant
Location: chr20:3912578 (GRCh38)
Gene constraint: LOEUF 1.115 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.99 · 1 PDB
Residue 342: an α-helix

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.Asp342Ala Likely pathogenic ★ same residue
PANK2 p.Asp342Val Likely pathogenic ★ same residue
PANK2 p.Asp342Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
PANK2 p.Asp342Tyr Conflicting classifications of pathogenicity ★ ⚠ 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

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-asp342 (accessed [today's date]).

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