Is GNPTAB p.Ser643= (c.1929T>G) pathogenic?

GNPTAB p.Ser643= (c.1929T>G) is classified Likely benign in GNPTAB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-25). Ultra-rare (popmax 0.078%, eas); Associated with Inborn genetic diseases.

What condition is associated with GNPTAB p.Ser643= (c.1929T>G)?

GNPTAB p.Ser643= (c.1929T>G) is associated with Inborn genetic diseases, mucolipidosis type II, mucolipidosis type III, alpha/beta (ClinVar).

How common is GNPTAB p.Ser643= (c.1929T>G) in the general population?

GNPTAB p.Ser643= (c.1929T>G) is ultra-rare (popmax 0.078%, eas) (gnomAD).

GNPTAB p.Ser643=

c.1929T>G · rs199921889 · VCV725206

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.078%, eas)

Conditions

Inborn genetic diseases

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 -1.2	GERP -3.8
Overall
CADD	0.654	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.078% East Asian · 35/44,888 alleles

Filtering AF 0.0576% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0506%

Overall 0.00273% 44/1,614,128 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.078%	1,283
Remaining individualsnot grpmax-eligible	0.0016%	62,508
South Asian	0.0011%	91,074
European (non-Finnish)	0.000593%	168,567

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.Ser643=
Coding: c.1929T>G
MANE Select: NM_024312
dbSNP: rs199921889
Type: single nucleotide variant
Location: chr12:101764988 (GRCh38)
Gene constraint: LOEUF 0.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.15 · 5 PDB
Residue 643: a UniProt-annotated variant site (in mliiia)

Full GNPTAB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mucolipidosis type II mucolipidosis type III, alpha/beta

Similar variants

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
GNPTAB c.324-2A>G Likely 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-ser643 (accessed [today's date]).

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