Is GNPTAB p.Ser55fs (c.163dup) pathogenic?

GNPTAB p.Ser55fs (c.163dup) is classified Likely pathogenic in GNPTAB (ClinVar, Single submitter, 2 submitters; last evaluated 2024-04-30). Very rare (popmax 0.00133%, afr); Associated with mucolipidosis type II.

What condition is associated with GNPTAB p.Ser55fs (c.163dup)?

GNPTAB p.Ser55fs (c.163dup) is associated with mucolipidosis type II (ClinVar).

How common is GNPTAB p.Ser55fs (c.163dup) in the general population?

GNPTAB p.Ser55fs (c.163dup) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Mucolipidosis type II inherited?

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

GNPTAB p.Ser55fs

c.163dup · rs281864949 · VCV39037

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 2 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.4	GERP 2.5, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,914 alleles

Overall 6.2e-05% 1/1,612,588 alleles · very rare exomes 1/1,460,534 · genomes 0/152,054 · 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: GNPTAB
Protein: p.Ser55fs
Coding: c.163dup
MANE Select: NM_024312
dbSNP: rs281864949
Type: Duplication
Location: chr12:101796716 (GRCh38)
Gene constraint: LOEUF 0.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.15 · 5 PDB
Residue 55: an α-helix

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.Ser55= Likely benign ★ 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-ser55fs (accessed [today's date]).

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