Is GNPTAB p.Ser385= (c.1155A>C) pathogenic?

GNPTAB p.Ser385= (c.1155A>C) is classified Conflicting classifications of pathogenicity in GNPTAB (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-26). Rare (popmax 0.113%, sas); Associated with mucolipidosis type III, alpha/beta.

What condition is associated with GNPTAB p.Ser385= (c.1155A>C)?

GNPTAB p.Ser385= (c.1155A>C) is associated with mucolipidosis type III, alpha/beta, mucolipidosis type II (ClinVar).

How common is GNPTAB p.Ser385= (c.1155A>C) in the general population?

GNPTAB p.Ser385= (c.1155A>C) is rare (popmax 0.113%, sas) (gnomAD).

How is Mucolipidosis type III inherited?

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

GNPTAB p.Ser385=

c.1155A>C · rs754258764 · VCV306811

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.113%, sas)

Conditions

mucolipidosis type III, alpha/beta

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 -0.64	GERP -2.4, phastCons 0.04
Overall
CADD	9.653	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.113% South Asian · 103/91,084 alleles

Filtering AF 0.0953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0888%

Overall 0.00669% 108/1,613,968 alleles · rare exomes 103/1,461,878 · genomes 5/152,090 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.113%	884
Middle Eastern	0.0329%	3,042
Remaining individualsnot grpmax-eligible	0.0048%	20,827

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.Ser385=
Coding: c.1155A>C
MANE Select: NM_024312
dbSNP: rs754258764
Type: single nucleotide variant
Location: chr12:101770150 (GRCh38)
Gene constraint: LOEUF 0.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.15 · 5 PDB
Residue 385: an α-helix; a UniProt-annotated variant site (in mliiia); a UniProt-annotated variant site (in mlii; no loss of golgi localization; no defects in protein cleavage into alpha and beta subunits; loss of udp-n-acetylglucosamine-lysosomal-enzyme n-acetylglucosaminephosphotransferase activity)

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.Ser385Ter Likely pathogenic ★ same residue
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

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-ser385 (accessed [today's date]).

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