Is GNPTAB p.Arg1237Gln (c.3710G>A) pathogenic?

GNPTAB p.Arg1237Gln (c.3710G>A) is classified Conflicting classifications of pathogenicity in GNPTAB (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-11). AlphaMissense: likely benign (0.1681); Ultra-rare (popmax 0.0962%, eas); Associated with mucolipidosis type II.

What condition is associated with GNPTAB p.Arg1237Gln (c.3710G>A)?

GNPTAB p.Arg1237Gln (c.3710G>A) is associated with mucolipidosis type II, mucolipidosis type III, alpha/beta (ClinVar).

How common is GNPTAB p.Arg1237Gln (c.3710G>A) in the general population?

GNPTAB p.Arg1237Gln (c.3710G>A) is ultra-rare (popmax 0.0962%, eas) (gnomAD).

How is Mucolipidosis type II inherited?

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

What do computational predictors say about GNPTAB p.Arg1237Gln (c.3710G>A)?

AlphaMissense predicts likely benign (score 0.1681) — an in-silico prediction, not a clinical call.

GNPTAB p.Arg1237Gln

c.3710G>A · rs150841760 · VCV306793

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1681 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0962%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

mucolipidosis type II

Computational evidence

Protein change
AlphaMissense	0.1681	likely benign
REVEL	0.619	indeterminate
SaProt	LLR -7.33	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 84 kb · p 4.2e-05 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0962% East Asian · 43/44,694 alleles

Filtering AF 0.0734% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0653%

Overall 0.00962% 152/1,580,260 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0962%	1,039
Remaining individualsnot grpmax-eligible	0.0766%	1,306
Finnishnot grpmax-eligible	0.0438%	2,283
African / African-American	0.0202%	4,946
South Asian	0.00553%	18,068
Admixed American	0.00167%	59,924
European (non-Finnish)	0.00113%	88,420

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.Arg1237Gln
Coding: c.3710G>A
MANE Select: NM_024312
dbSNP: rs150841760
Type: single nucleotide variant
Location: chr12:101747225 (GRCh38)
Gene constraint: LOEUF 0.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.15 · 5 PDB
Residue 1237: a UniProt-annotated variant site (in mliiia); a UniProt-annotated variant site (in mlii)

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.Arg1237= 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
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-arg1237gln (accessed [today's date]).

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