Is GALNS p.Phe69Val (c.205T>G) pathogenic?

GALNS p.Phe69Val (c.205T>G) is classified Uncertain significance in GALNS (ClinVar, Single submitter, 2 submitters; last evaluated 2021-02-01). AlphaMissense: ambiguous (0.5431); Absent from gnomAD v4.1; Associated with mucopolysaccharidosis type 4A.

What condition is associated with GALNS p.Phe69Val (c.205T>G)?

GALNS p.Phe69Val (c.205T>G) is associated with mucopolysaccharidosis type 4A (ClinVar).

How common is GALNS p.Phe69Val (c.205T>G) in the general population?

GALNS p.Phe69Val (c.205T>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.Phe69Val (c.205T>G)?

AlphaMissense predicts ambiguous (score 0.5431) — an in-silico prediction, not a clinical call.

GALNS p.Phe69Val

c.205T>G · rs118204445 · VCV710

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5431 · 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	0.5431	ambiguous
REVEL	0.869	moderately pathogenic-leaning
SaProt	LLR -9.91	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 6.9	GERP 0.51, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 42 kb · p 0.0044 · regional, not allelic
Overall
CADD	24.3	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.Phe69Val
Coding: c.205T>G
MANE Select: NM_000512
dbSNP: rs118204445
Type: single nucleotide variant
Location: chr16:88842745 (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 69: 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 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-phe69val (accessed [today's date]).

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