Is GALNS p.Ala6= (c.18G>T) pathogenic?

GALNS p.Ala6= (c.18G>T) is classified Likely benign in GALNS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-27). Very rare (popmax 0.0027%, eas); Associated with mucopolysaccharidosis type 4A.

What condition is associated with GALNS p.Ala6= (c.18G>T)?

GALNS p.Ala6= (c.18G>T) is associated with mucopolysaccharidosis type 4A (ClinVar).

How common is GALNS p.Ala6= (c.18G>T) in the general population?

GALNS p.Ala6= (c.18G>T) is very rare (popmax 0.0027%, eas) (gnomAD).

How is Mucopolysaccharidosis type 4 inherited?

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

GALNS p.Ala6=

c.18G>T · rs753547371 · VCV2794084

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0027%, eas)

Conditions

mucopolysaccharidosis type 4A

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 -0.7	GERP -2.4
Overall
CADD	11.58	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0027% East Asian · 1/37,084 alleles

Overall 6.62e-05% 1/1,509,988 alleles · very rare exomes 1/1,358,268 · genomes 0/151,720 · 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.Ala6=
Coding: c.18G>T
MANE Select: NM_000512
dbSNP: rs753547371
Type: single nucleotide variant
Location: chr16:88856860 (GRCh38)
Gene constraint: LOEUF 1.251 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.04 · 2 PDB

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 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
GALNS c.1365-1G>C Pathogenic ★★ same condition
GALNS c.244+1G>A 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-ala6 (accessed [today's date]).

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