Is GALNS p.Val239Phe (c.715G>T) pathogenic?

GALNS p.Val239Phe (c.715G>T) is classified Conflicting classifications of pathogenicity in GALNS (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-01-17). AlphaMissense: ambiguous (0.527); Absent from gnomAD v4.1; Associated with mucopolysaccharidosis type 4A.

What condition is associated with GALNS p.Val239Phe (c.715G>T)?

GALNS p.Val239Phe (c.715G>T) is associated with mucopolysaccharidosis type 4A (ClinVar).

How common is GALNS p.Val239Phe (c.715G>T) in the general population?

GALNS p.Val239Phe (c.715G>T) 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.Val239Phe (c.715G>T)?

AlphaMissense predicts ambiguous (score 0.527) — an in-silico prediction, not a clinical call.

GALNS p.Val239Phe

c.715G>T · rs145131011 · VCV1048205

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.527 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

mucopolysaccharidosis type 4A

Computational evidence

Protein change
AlphaMissense	0.527	ambiguous
REVEL	0.747	pathogenic-leaning
SaProt	LLR -7.78	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 2.6	GERP 1.5, phastCons 0.99
Regional constraint	o/e 1.11	unconstrained · MANE · 42 kb · p 0.0044 · regional, not allelic
Overall
CADD	21.2	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

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.Val239Phe
Coding: c.715G>T
MANE Select: NM_000512
dbSNP: rs145131011
Type: single nucleotide variant
Location: chr16:88835768 (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 239: the 'catalytic domain' region; a UniProt-annotated variant site (in mps4a)

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.Val239Ile Uncertain significance ★★ ⚠ same residue
GALNS p.Val239Gly Likely pathogenic ★ ⚠ same residue
GALNS p.Val239= Likely benign ★ same residue
GALNS p.Val239fs 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
GALNS c.1242+1G>C 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-val239phe (accessed [today's date]).

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