Is PANK2 p.Arg3Ser (c.9G>T) pathogenic?

PANK2 p.Arg3Ser (c.9G>T) is classified Uncertain significance in PANK2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-07-02). AlphaMissense: likely benign (0.186); Very rare (popmax 0.000129%); Associated with Inborn genetic diseases.

What condition is associated with PANK2 p.Arg3Ser (c.9G>T)?

PANK2 p.Arg3Ser (c.9G>T) is associated with Inborn genetic diseases, pantothenate kinase-associated neurodegeneration (ClinVar).

How common is PANK2 p.Arg3Ser (c.9G>T) in the general population?

PANK2 p.Arg3Ser (c.9G>T) is very rare (popmax 0.000129%) (gnomAD).

What do computational predictors say about PANK2 p.Arg3Ser (c.9G>T)?

AlphaMissense predicts likely benign (score 0.186) — an in-silico prediction, not a clinical call.

PANK2 p.Arg3Ser

c.9G>T · rs1211425299 · VCV567543

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.186 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000129%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.186	likely benign
REVEL	0.179	moderately benign-leaning
SaProt	LLR -6.15	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -2, phastCons 0.14
Overall
CADD	6.529	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000129%

Overall 0.000129% 2/1,546,630 alleles · very rare exomes 2/1,394,310 · genomes 0/152,320 · 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.Arg3Ser
Coding: c.9G>T
MANE Select: NM_001386393 · reported on NM_153638
dbSNP: rs1211425299
Type: single nucleotide variant
Location: chr20:3889109 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pantothenate kinase-associated neurodegeneration

Similar variants

PANK2 p.Arg3= 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
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-arg3ser (accessed [today's date]).

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