Is GNPTAB p.Asp58= (c.174C>T) pathogenic?

GNPTAB p.Asp58= (c.174C>T) is classified Conflicting classifications of pathogenicity in GNPTAB (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-25). Very rare (popmax 0.009%, nfe); Associated with mucolipidosis type II.

What condition is associated with GNPTAB p.Asp58= (c.174C>T)?

GNPTAB p.Asp58= (c.174C>T) is associated with mucolipidosis type II, mucolipidosis type III, alpha/beta (ClinVar).

How common is GNPTAB p.Asp58= (c.174C>T) in the general population?

GNPTAB p.Asp58= (c.174C>T) is very rare (popmax 0.009%, nfe) (gnomAD).

How is Mucolipidosis type II inherited?

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

GNPTAB p.Asp58=

c.174C>T · rs148948607 · VCV725375

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.009%, nfe)

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 3.2	GERP 0.81, phastCons 1
Overall
CADD	9.341	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.009% European (non-Finnish) · 106/1,178,184 alleles

Filtering AF 0.00758% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00707%

Overall 0.0488% 786/1,611,724 alleles · very rare exomes 703/1,459,610 · genomes 83/152,114 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.99%	50
Remaining individualsnot grpmax-eligible	0.139%	718
European (non-Finnish)grpmax	0.009%	11,115
Admixed American	0.005%	19,997
African / African-American	0.00267%	37,426

Ashkenazi Jewish 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.Asp58=
Coding: c.174C>T
MANE Select: NM_024312
dbSNP: rs148948607
Type: single nucleotide variant
Location: chr12:101796706 (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

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 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
GNPTAB c.2715+2T>G Pathogenic ★★ same condition
GNPTAB c.324-2A>G 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-asp58 (accessed [today's date]).

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