Is PANK2 c.2T>A pathogenic?

PANK2 c.2T>A is classified Benign/Likely benign in PANK2 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0818); Common (popmax 15.4%, amr) — too common for a highly-penetrant pathogenic allele; Associated with pantothenate kinase-associated neurodegeneration.

What condition is associated with PANK2 c.2T>A?

PANK2 c.2T>A is associated with pantothenate kinase-associated neurodegeneration (ClinVar).

What do computational predictors say about PANK2 c.2T>A?

AlphaMissense predicts likely benign (score 0.0818) — an in-silico prediction, not a clinical call.

PANK2 c.2T>A

Q: How common is PANK2 c.2T>A in the general population?

PANK2 c.2T>A is common (popmax 15.4%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Pantothenate kinase-associated neurodegeneration inherited?

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

rs71647828 · VCV193506

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

AlphaMissense

likely benign

0.0818 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 15.4%, amr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

pantothenate kinase-associated neurodegeneration

Computational evidence

Protein change
AlphaMissense	0.0818	likely benign
REVEL	0.437	indeterminate
SaProt	LLR -7.65	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.8	GERP 1.7, phastCons 1
Overall
CADD	20.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 15.4% Admixed American · 8,281/53,798 alleles

Filtering AF 15.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 15%

Overall 6.1% 95,333/1,562,410 alleles · common exomes 84,766/1,410,130 · genomes 10,567/152,280 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	15.4%	6
East Asian	12.3%	8
Middle Eastern	8.34%	12
Finnishnot grpmax-eligible	7.88%	13
Remaining individualsnot grpmax-eligible	6.56%	15
Ashkenazi Jewishnot grpmax-eligible	6.31%	16
African / African-American	6.1%	16
Amishnot grpmax-eligible	5.82%	17
European (non-Finnish)	5.57%	18
South Asian	2.87%	35

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
Coding: c.2T>A
MANE Select: NM_001386393
dbSNP: rs71647828
Type: single nucleotide variant
Location: chr20:3889432 (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 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
PANK2 p.Arg154Trp 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-c-2t-a (accessed [today's date]).

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