Is GNPTAB p.Phe53fs (c.157_160del) pathogenic?

GNPTAB p.Phe53fs (c.157160del) is classified Pathogenic/Likely pathogenic in GNPTAB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-14). Very rare (popmax 0.0011%, nfe); Associated with mucolipidosis type II.

What condition is associated with GNPTAB p.Phe53fs (c.157_160del)?

GNPTAB p.Phe53fs (c.157_160del) is associated with mucolipidosis type II, mucolipidosis type III, alpha/beta (ClinVar).

How common is GNPTAB p.Phe53fs (c.157_160del) in the general population?

GNPTAB p.Phe53fs (c.157_160del) is very rare (popmax 0.0011%, nfe) (gnomAD).

How is Mucolipidosis type II inherited?

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

GNPTAB p.Phe53fs

c.157_160del · rs794727302 · VCV195376

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

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 7.7	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 0.0011% European (non-Finnish) · 13/1,179,440 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000868% 14/1,613,272 alleles · very rare exomes 14/1,460,966 · genomes 0/152,306 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)grpmax	0.0011%	90,726

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe53fs
Coding: c.157_160del
MANE Select: NM_024312
dbSNP: rs794727302
Type: Microsatellite
Location: chr12:101796720 (GRCh38)
Gene constraint: LOEUF 0.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.15 · 5 PDB
Residue 53: 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

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.Asn859fs Pathogenic ★★ same condition
GNPTAB p.Glu1187fs Pathogenic/Likely pathogenic ★★ same condition
GNPTAB p.Glu127fs Likely pathogenic ★★ same condition
GNPTAB p.Glu833fs Pathogenic/Likely pathogenic ★★ same condition
GNPTAB p.Leu1168fs Pathogenic ★★ same condition
GNPTAB p.Lys850fs Pathogenic/Likely pathogenic ★★ same condition
GNPTAB p.Met957fs Pathogenic ★★ same condition
GNPTAB p.Ser654fs 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-phe53fs (accessed [today's date]).

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