Is PANK2 p.Asp342Val (c.1025A>T) pathogenic?

PANK2 p.Asp342Val (c.1025A>T) is classified Likely pathogenic in PANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). AlphaMissense: likely pathogenic (0.9979); Very rare (popmax 8.47e-05%, nfe); Associated with pantothenate kinase-associated neurodegeneration.

What condition is associated with PANK2 p.Asp342Val (c.1025A>T)?

PANK2 p.Asp342Val (c.1025A>T) is associated with pantothenate kinase-associated neurodegeneration (ClinVar).

How common is PANK2 p.Asp342Val (c.1025A>T) in the general population?

PANK2 p.Asp342Val (c.1025A>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about PANK2 p.Asp342Val (c.1025A>T)?

AlphaMissense predicts likely pathogenic (score 0.9979) — an in-silico prediction, not a clinical call.

PANK2 p.Asp342Val

Q: How is Pantothenate kinase-associated neurodegeneration inherited?

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

c.1025A>T · rs763496520 · VCV3001570

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9979 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

pantothenate kinase-associated neurodegeneration

Computational evidence

Protein change
AlphaMissense	0.9979	likely pathogenic ✓ concordant with ClinVar · top 6% in PANK2
REVEL	0.958	strongly pathogenic-leaning
SaProt	LLR -17.23	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 29 kb · p 0.51 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D452V vs ClinVar D342V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

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

Overall 6.2e-05% 1/1,613,952 alleles · very rare exomes 0/1,461,892 · genomes 1/152,060 · 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.Asp342Val
Coding: c.1025A>T
MANE Select: NM_001386393
dbSNP: rs763496520
Type: single nucleotide variant
Location: chr20:3912577 (GRCh38)
Gene constraint: LOEUF 1.115 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.99 · 1 PDB
Residue 452 UniProt numbering: 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.Asp342Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
PANK2 p.Asp342Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
PANK2 p.Asp342= Likely benign ★ 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-asp342val (accessed [today's date]).

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