Is GNPTAB p.Trp416fs (c.1246dup) pathogenic?

GNPTAB p.Trp416fs (c.1246dup) is classified Pathogenic in GNPTAB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-10). No gnomAD frequency available for this variant; Associated with mucolipidosis type III, alpha/beta.

What condition is associated with GNPTAB p.Trp416fs (c.1246dup)?

GNPTAB p.Trp416fs (c.1246dup) is associated with mucolipidosis type III, alpha/beta, mucolipidosis type II (ClinVar).

How common is GNPTAB p.Trp416fs (c.1246dup) in the general population?

GNPTAB p.Trp416fs (c.1246dup) is no gnomAD frequency available for this variant (gnomAD).

How is Mucolipidosis type III inherited?

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

GNPTAB p.Trp416fs

c.1246dup · rs2547960923 · VCV2096174

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

mucolipidosis type III, alpha/beta

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.7	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GNPTAB
Protein: p.Trp416fs
Coding: c.1246dup
MANE Select: NM_024312
dbSNP: rs2547960923
Type: Duplication
Location: chr12:101770058 (GRCh38)
Gene constraint: LOEUF 0.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.15 · 5 PDB
Residue 416: a UniProt-annotated variant site (in mliiia)

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

Disease context

mucolipidosis type III, alpha/beta — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mucolipidosis type II

For Mucolipidosis type III (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

GNPTAB p.Trp416Ter Pathogenic ★ same residue
GNPTAB p.Arg680fs Pathogenic/Likely pathogenic ★★ same condition
GNPTAB p.Asn1109fs Pathogenic ★★ same condition
GNPTAB p.Asn175fs Pathogenic/Likely pathogenic ★★ same condition
GNPTAB p.Asn250fs Pathogenic/Likely pathogenic ★★ same condition
GNPTAB p.Asn351fs Pathogenic/Likely pathogenic ★★ same condition
GNPTAB p.Asn750fs Pathogenic ★★ same condition
GNPTAB p.Leu1054fs 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/gnptab-p-trp416fs (accessed [today's date]).

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