Is GNPTG p.Pro44Ala (c.130C>G) pathogenic?

GNPTG p.Pro44Ala (c.130C>G) is classified Uncertain significance in GNPTG (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-12-28). AlphaMissense: likely benign (0.1072); Ultra-rare (popmax 0.0178%, afr); Associated with Inborn genetic diseases.

What condition is associated with GNPTG p.Pro44Ala (c.130C>G)?

GNPTG p.Pro44Ala (c.130C>G) is associated with Inborn genetic diseases, GNPTG-mucolipidosis (ClinVar).

How common is GNPTG p.Pro44Ala (c.130C>G) in the general population?

GNPTG p.Pro44Ala (c.130C>G) is ultra-rare (popmax 0.0178%, afr) (gnomAD).

What do computational predictors say about GNPTG p.Pro44Ala (c.130C>G)?

AlphaMissense predicts likely benign (score 0.1072) — an in-silico prediction, not a clinical call.

GNPTG p.Pro44Ala

c.130C>G · rs771564346 · VCV964872

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1072 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1072	likely benign
REVEL	0.158	moderately benign-leaning
SaProt	LLR -7.50	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.7, phastCons 1
Regional constraint	o/e 1.33	unconstrained · MANE · 11 kb · p 1.1e-11 · regional, not allelic
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% African / African-American · 13/72,994 alleles

Filtering AF 0.0105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00832%

Overall 0.00271% 42/1,548,510 alleles · ultra-rare exomes 31/1,396,308 · genomes 11/152,202 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0178%	5,615
European (non-Finnish)	0.00235%	42,479
Remaining individualsnot grpmax-eligible	0.00167%	59,894
South Asian	0.00119%	83,990

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: GNPTG
Protein: p.Pro44Ala
Coding: c.130C>G
MANE Select: NM_032520
dbSNP: rs771564346
Type: single nucleotide variant
Location: chr16:1352258 (GRCh38)
Gene constraint: LOEUF 1.369 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.63

Full GNPTG 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: GNPTG-mucolipidosis

Similar variants

GNPTG p.Pro44Thr Uncertain significance ★ ⚠ same residue
GNPTG c.179-1G>A Likely pathogenic ★★ same condition
GNPTG c.233+1G>A Pathogenic/Likely pathogenic ★★ same condition
GNPTG c.234-1G>A Pathogenic/Likely pathogenic ★★ same condition
GNPTG c.234-1G>C Pathogenic ★★ same condition
GNPTG c.318-1G>A Pathogenic ★★ same condition
GNPTG c.52+1G>C Likely pathogenic ★★ same condition
GNPTG c.526+2T>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/gnptg-p-pro44ala (accessed [today's date]).

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