Is GNPTAB p.Arg46= (c.136C>A) pathogenic?

GNPTAB p.Arg46= (c.136C>A) is classified Benign/Likely benign in GNPTAB (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Low-frequency (popmax 3.19%, afr); Associated with mucolipidosis type II.

What condition is associated with GNPTAB p.Arg46= (c.136C>A)?

GNPTAB p.Arg46= (c.136C>A) is associated with mucolipidosis type II, mucolipidosis type III, alpha/beta (ClinVar).

How common is GNPTAB p.Arg46= (c.136C>A) in the general population?

GNPTAB p.Arg46= (c.136C>A) is low-frequency (popmax 3.19%, afr) (gnomAD).

How is Mucolipidosis type II inherited?

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

GNPTAB p.Arg46=

c.136C>A · rs78347057 · VCV235510

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.19%, afr)

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 4.9	GERP 0.003, phastCons 1
Overall
CADD	8.453	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.19% African / African-American · 2,387/74,846 alleles

Filtering AF 3.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.04%

Overall 0.171% 2,754/1,611,930 alleles · low-frequency exomes 1,320/1,459,914 · genomes 1,434/152,016 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.19%	31
Remaining individualsnot grpmax-eligible	0.285%	351
Admixed American	0.25%	400
Middle Eastern	0.0661%	1,514
South Asian	0.00439%	22,756
European (non-Finnish)	0.00263%	38,019

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.Arg46=
Coding: c.136C>A
MANE Select: NM_024312
dbSNP: rs78347057
Type: single nucleotide variant
Location: chr12:101796744 (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 p.Arg46Ter Pathogenic ★★ same residue
GNPTAB p.Arg46Gln Benign/Likely benign ★★ 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

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-arg46 (accessed [today's date]).

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