Is GALNS p.Pro484Ser (c.1450C>T) pathogenic?

GALNS p.Pro484Ser (c.1450C>T) is classified Conflicting classifications of pathogenicity in GALNS (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-06-24). AlphaMissense: ambiguous (0.3439); Very rare (popmax 0.00115%, sas); Associated with mucopolysaccharidosis type 4.

What condition is associated with GALNS p.Pro484Ser (c.1450C>T)?

GALNS p.Pro484Ser (c.1450C>T) is associated with mucopolysaccharidosis type 4, mucopolysaccharidosis type 4A (ClinVar).

How common is GALNS p.Pro484Ser (c.1450C>T) in the general population?

GALNS p.Pro484Ser (c.1450C>T) is very rare (popmax 0.00115%, sas) (gnomAD).

How is Mucopolysaccharidosis type 4 inherited?

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

What do computational predictors say about GALNS p.Pro484Ser (c.1450C>T)?

AlphaMissense predicts ambiguous (score 0.3439) — an in-silico prediction, not a clinical call.

GALNS p.Pro484Ser

c.1450C>T · rs1204485789 · VCV1048241

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.3439 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00115%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

mucopolysaccharidosis type 4

Computational evidence

Protein change
AlphaMissense	0.3439	ambiguous
REVEL	0.816	moderately pathogenic-leaning
SaProt	LLR -7.53	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 42 kb · p 0.0044 · regional, not allelic
Overall
CADD	25.2	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 0.00115% South Asian · 1/87,130 alleles

Overall 6.32e-05% 1/1,582,322 alleles · very rare exomes 1/1,429,984 · genomes 0/152,338 · 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: GALNS
Protein: p.Pro484Ser
Coding: c.1450C>T
MANE Select: NM_000512
dbSNP: rs1204485789
Type: single nucleotide variant
Location: chr16:88818039 (GRCh38)
Gene constraint: LOEUF 1.251 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.04 · 2 PDB
Residue 484: a UniProt-annotated variant site (in mps4a); an α-helix

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

Disease context

mucopolysaccharidosis type 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mucopolysaccharidosis type 4A

For Mucopolysaccharidosis type 4 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy
Prevalence: <1 / 1 000 000 (Sweden)

Similar variants

GALNS p.Pro484Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
GALNS p.Pro484His Uncertain significance ★ ⚠ same residue
GALNS c.1139+1G>A Pathogenic ★★ same condition
GALNS c.121-1G>A Pathogenic ★★ same condition
GALNS c.121-2A>G Pathogenic/Likely pathogenic ★★ same condition
GALNS c.1242+1G>C Pathogenic/Likely pathogenic ★★ same condition
GALNS c.1243-2A>C Likely pathogenic ★★ same condition
GALNS c.1364+1G>A 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/galns-p-pro484ser (accessed [today's date]).

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