Is GNPTAB p.Pro173fs (c.518del) pathogenic?

GNPTAB p.Pro173fs (c.518del) is classified Pathogenic in GNPTAB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-09). Absent from gnomAD; Associated with mucolipidosis type II.

What condition is associated with GNPTAB p.Pro173fs (c.518del)?

GNPTAB p.Pro173fs (c.518del) is associated with mucolipidosis type II (ClinVar).

How common is GNPTAB p.Pro173fs (c.518del) in the general population?

GNPTAB p.Pro173fs (c.518del) is absent from gnomAD (gnomAD).

How is Mucolipidosis type II inherited?

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

GNPTAB p.Pro173fs

c.518del · rs2137144428 · VCV1679880

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 II

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 5 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.8	GERP -3.5

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.Pro173fs
Coding: c.518del
MANE Select: NM_024312
dbSNP: rs2137144428
Type: Deletion
Location: chr12:101786065 (GRCh38)
Gene constraint: LOEUF 0.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.15 · 5 PDB

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

For Mucolipidosis type II (Orphanet):

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

Similar variants

GNPTAB p.Pro173= Likely benign ★ same residue
GNPTAB c.2915+4_2915+9del Likely pathogenic ★★ same condition
GNPTAB p.Ala34fs Pathogenic/Likely pathogenic ★★ same condition
GNPTAB p.Asn1093_Cys1094insTer Pathogenic/Likely pathogenic ★★ same condition
GNPTAB p.Asn148fs Pathogenic ★★ same condition
GNPTAB p.Asp467fs Pathogenic ★★ same condition
GNPTAB p.Asp919fs Pathogenic/Likely pathogenic ★★ same condition
GNPTAB p.Cys528fs 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-pro173fs (accessed [today's date]).

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