Is GNPTAB p.Ile403= (c.1209T>C) pathogenic?

GNPTAB p.Ile403= (c.1209T>C) is classified Likely benign in GNPTAB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-02). Very rare (popmax 0.00223%, eas); Associated with mucolipidosis type II.

What condition is associated with GNPTAB p.Ile403= (c.1209T>C)?

GNPTAB p.Ile403= (c.1209T>C) is associated with mucolipidosis type II, mucolipidosis type III, alpha/beta (ClinVar).

How common is GNPTAB p.Ile403= (c.1209T>C) in the general population?

GNPTAB p.Ile403= (c.1209T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Mucolipidosis type II inherited?

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

GNPTAB p.Ile403=

c.1209T>C · rs947905285 · VCV792235

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

mucolipidosis type II

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.93	GERP -3.8, phastCons 0.99
Overall
CADD	8.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,890 alleles

Overall 6.84e-05% 1/1,461,866 alleles · very rare

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: GNPTAB
Protein: p.Ile403=
Coding: c.1209T>C
MANE Select: NM_024312
dbSNP: rs947905285
Type: single nucleotide variant
Location: chr12:101770096 (GRCh38)
Gene constraint: LOEUF 0.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.15 · 5 PDB
Residue 403: a β-strand; a UniProt-annotated variant site (in mliiia); a UniProt-annotated variant site (in mliiia; loss of localization to the golgi; loss of protein cleavage into alpha and beta subunits; decreased udp-n-acetylglucosamine-lysosomal-enzyme n-acetylglucosaminephosphotransferase activity)

Full GNPTAB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mucolipidosis type II — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mucolipidosis type III, alpha/beta

For Mucolipidosis type II (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

GNPTAB p.Ile403Thr Pathogenic ★★ same residue
GNPTAB p.Ile403Met Uncertain significance ★ ⚠ same residue
GNPTAB c.118-1G>A Pathogenic/Likely pathogenic ★★ same condition
GNPTAB c.118-2A>G Pathogenic/Likely pathogenic ★★ same condition
GNPTAB c.1284+1G>T Pathogenic/Likely pathogenic ★★ same condition
GNPTAB c.1408+1G>T Pathogenic/Likely pathogenic ★★ same condition
GNPTAB c.1409-2A>G Pathogenic/Likely pathogenic ★★ same condition
GNPTAB c.2715+1G>A 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/gnptab-p-ile403 (accessed [today's date]).

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