Is GALNS p.Ser82= (c.246G>A) pathogenic?

GALNS p.Ser82= (c.246G>A) is classified Likely benign in GALNS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-13). Very rare (popmax 0.00884%, sas); Associated with mucopolysaccharidosis type 4A.

What condition is associated with GALNS p.Ser82= (c.246G>A)?

GALNS p.Ser82= (c.246G>A) is associated with mucopolysaccharidosis type 4A (ClinVar).

How common is GALNS p.Ser82= (c.246G>A) in the general population?

GALNS p.Ser82= (c.246G>A) is very rare (popmax 0.00884%, sas) (gnomAD).

How is Mucopolysaccharidosis type 4 inherited?

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

GALNS p.Ser82=

c.246G>A · rs370437841 · VCV2715183

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00884%, sas)

Conditions

mucopolysaccharidosis type 4A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.007	strongly benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.33	GERP -3.4, phastCons 0.022
Overall
CADD	5.029	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00884% South Asian · 8/90,548 alleles

Filtering AF 0.00439% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00314%

Overall 0.0013% 21/1,611,802 alleles · very rare exomes 21/1,459,490 · genomes 0/152,312 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00884%	11,319
Finnishnot grpmax-eligible	0.00627%	15,941
East Asian	0.00446%	22,417
Remaining individualsnot grpmax-eligible	0.0016%	62,390
European (non-Finnish)	0.000509%	196,503

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.Ser82=
Coding: c.246G>A
MANE Select: NM_000512
dbSNP: rs370437841
Type: single nucleotide variant
Location: chr16:88841970 (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 82: an α-helix; the 'catalytic domain' region

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.Ser82Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
GALNS p.Ser82Pro 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-ser82 (accessed [today's date]).

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