Is GNPTAB p.Asp190Val (c.569A>T) pathogenic?

GNPTAB p.Asp190Val (c.569A>T) is classified Pathogenic/Likely pathogenic in GNPTAB (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-02-28). AlphaMissense: likely benign (0.0879); Very rare (popmax 0.00134%, afr); Associated with mucolipidosis type II.

What condition is associated with GNPTAB p.Asp190Val (c.569A>T)?

GNPTAB p.Asp190Val (c.569A>T) is associated with mucolipidosis type II, mucopolysaccharidosis type 3A, mucolipidosis type III, alpha/beta (ClinVar).

How common is GNPTAB p.Asp190Val (c.569A>T) in the general population?

GNPTAB p.Asp190Val (c.569A>T) is very rare (popmax 0.00134%, afr) (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.Asp190Val (c.569A>T)?

AlphaMissense predicts likely benign (score 0.0879) — an in-silico prediction, not a clinical call.

GNPTAB p.Asp190Val

c.569A>T · rs34946266 · VCV38431

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0879 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

mucolipidosis type II

Computational evidence

Protein change
AlphaMissense	0.0879	likely benign ⚠ discordant with ClinVar
REVEL	0.632	indeterminate
SaProt	LLR -8.78	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.96	donor gain · deltas
Pangolin	Δ0.80	gain · loss 0.77 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.3	GERP 0.51, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 84 kb · p 4.2e-05 · regional, not allelic
Overall
CADD	25.8	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 0.00134% African / African-American · 1/74,758 alleles

Filtering AF 0.000294% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000212%

Overall 0.000623% 10/1,604,824 alleles · very rare exomes 9/1,452,618 · genomes 1/152,206 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00161%	62,128
African / African-Americangrpmax	0.00134%	74,758
European (non-Finnish)	0.000683%	146,463

Remaining individuals 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.Asp190Val
Coding: c.569A>T
MANE Select: NM_024312
dbSNP: rs34946266
Type: single nucleotide variant
Location: chr12:101786014 (GRCh38)
Gene constraint: LOEUF 0.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.15 · 5 PDB
Residue 190: a UniProt-annotated variant site (in mliiia; also found in patients with intermediate phenotype between mlii and mliiia; uncertain significance; no effect on protein abundance; no effect on localization to the golgi; no effect on protein cleavage into alpha and beta subunits; decreased udp-n-acetylglucosamine-lysosomal-enzyme n-acetylglucosaminephosphotransferase activity); an α-helix

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: mucopolysaccharidosis type 3A 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.Asp190Gly Uncertain significance ★ ⚠ 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-asp190val (accessed [today's date]).

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