Is GNPTAB p.Ser950= (c.2850G>A) pathogenic?

GNPTAB p.Ser950= (c.2850G>A) is classified Likely benign in GNPTAB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-17). Ultra-rare (popmax 0.0165%, mid); Associated with mucolipidosis type III, alpha/beta.

What condition is associated with GNPTAB p.Ser950= (c.2850G>A)?

GNPTAB p.Ser950= (c.2850G>A) is associated with mucolipidosis type III, alpha/beta, mucolipidosis type II (ClinVar).

How common is GNPTAB p.Ser950= (c.2850G>A) in the general population?

GNPTAB p.Ser950= (c.2850G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

How is Mucolipidosis type III inherited?

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

GNPTAB p.Ser950=

c.2850G>A · rs750905375 · VCV1640025

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 -0.57	GERP -3.8
Overall
CADD	1.365	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000494%

Overall 0.000616% 9/1,461,842 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
East Asian	0.00446%	22,436
African / African-American	0.004%	25,013
European (non-Finnish)	0.000254%	393,335

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.Ser950=
Coding: c.2850G>A
MANE Select: NM_024312
dbSNP: rs750905375
Type: single nucleotide variant
Location: chr12:101761629 (GRCh38)
Gene constraint: LOEUF 0.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.15 · 5 PDB
Residue 950: a UniProt-annotated variant site (in mliiia); a UniProt-annotated variant site (in mlii; abnormal protein cleavage into alpha and beta subunits; no effect on protein abundance; significantly decreased localization to the golgi; loss of udp-n-acetylglucosamine-lysosomal-enzyme n-acetylglucosaminephosphotransferase)

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.Ser950Ter 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-ser950 (accessed [today's date]).

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