Is GALNS p.Pro151Arg (c.452C>G) pathogenic?

GALNS p.Pro151Arg (c.452C>G) is classified Uncertain significance in GALNS (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-01). AlphaMissense: likely pathogenic (0.9416); Absent from gnomAD v4.1; Associated with mucopolysaccharidosis type 4A.

What condition is associated with GALNS p.Pro151Arg (c.452C>G)?

GALNS p.Pro151Arg (c.452C>G) is associated with mucopolysaccharidosis type 4A (ClinVar).

How common is GALNS p.Pro151Arg (c.452C>G) in the general population?

GALNS p.Pro151Arg (c.452C>G) is absent from gnomAD v4.1 (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.Pro151Arg (c.452C>G)?

AlphaMissense predicts likely pathogenic (score 0.9416) — an in-silico prediction, not a clinical call.

GALNS p.Pro151Arg

c.452C>G · rs559063128 · VCV1048461

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9416 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mucopolysaccharidosis type 4A

Computational evidence

Protein change
AlphaMissense	0.9416	likely pathogenic · top 10% in GALNS
REVEL	0.975	strongly pathogenic-leaning
SaProt	LLR -16.48	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 42 kb · p 0.0044 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GALNS
Protein: p.Pro151Arg
Coding: c.452C>G
MANE Select: NM_000512
dbSNP: rs559063128
Type: single nucleotide variant
Location: chr16:88837736 (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 151: an α-helix; the 'catalytic domain' region; a UniProt-annotated variant site (in mps4a; severe form)

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

Disease context

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

For Mucopolysaccharidosis type 4 (Orphanet):

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

Similar variants

GALNS p.Pro151Leu Pathogenic/Likely pathogenic ★★ same residue
GALNS p.Pro151Thr Pathogenic/Likely pathogenic ★★ same residue
GALNS p.Pro151Ser Uncertain significance ★ ⚠ same residue
GALNS p.Pro151= Likely benign ★ same residue
GALNS p.Pro151_Leu152insTer Pathogenic/Likely pathogenic ★★ 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

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-pro151arg (accessed [today's date]).

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