Is GNPTAB p.Val191= (c.573T>C) pathogenic?

GNPTAB p.Val191= (c.573T>C) is classified Likely benign in GNPTAB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-11). Very rare (popmax 0.00333%, amr); Associated with mucolipidosis type II.

What condition is associated with GNPTAB p.Val191= (c.573T>C)?

GNPTAB p.Val191= (c.573T>C) is associated with mucolipidosis type II, mucolipidosis type III, alpha/beta (ClinVar).

How common is GNPTAB p.Val191= (c.573T>C) in the general population?

GNPTAB p.Val191= (c.573T>C) is very rare (popmax 0.00333%, amr) (gnomAD).

How is Mucolipidosis type II inherited?

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

GNPTAB p.Val191=

c.573T>C · rs1157052984 · VCV1107943

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

mucolipidosis type II

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.25	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 0.26	GERP -3.5, phastCons 0.49
Overall
CADD	3.039	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,976 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000125% 2/1,600,208 alleles · very rare exomes 1/1,447,996 · genomes 1/152,212 · joint denominator

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.Val191=
Coding: c.573T>C
MANE Select: NM_024312
dbSNP: rs1157052984
Type: single nucleotide variant
Location: chr12:101780620 (GRCh38)
Gene constraint: LOEUF 0.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.15 · 5 PDB
Residue 191: 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: 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.Val191Ile 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-val191 (accessed [today's date]).

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