Is ARSA p.Gln488Ter (c.1462C>T) pathogenic?

ARSA p.Gln488Ter (c.1462C>T) is classified Pathogenic in ARSA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-11-07). Absent from gnomAD v4.1; Associated with ARYLSULFATASE A PSEUDODEFICIENCY.

What condition is associated with ARSA p.Gln488Ter (c.1462C>T)?

ARSA p.Gln488Ter (c.1462C>T) is associated with ARYLSULFATASE A PSEUDODEFICIENCY (ClinVar).

How common is ARSA p.Gln488Ter (c.1462C>T) in the general population?

ARSA p.Gln488Ter (c.1462C>T) is absent from gnomAD v4.1 (gnomAD).

ARSA p.Gln488Ter

c.1462C>T · rs74315482 · VCV3088

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,607,020)

Conditions

ARYLSULFATASE A PSEUDODEFICIENCY

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (8 of 8) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP 1.2, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,607,020). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ARSA
Protein: p.Gln488Ter
Coding: c.1462C>T
MANE Select: NM_000487
dbSNP: rs74315482
Type: single nucleotide variant
Location: chr22:50625213 (GRCh38)
Gene constraint: LOEUF 1.166 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.43 · 10 PDB
Residue 488: a disulfide bond

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

Disease context

ARYLSULFATASE A PSEUDODEFICIENCY — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARSA p.Gln488Arg Uncertain significance ★ same residue
ARSA p.Gln488= Likely benign ★ same residue
ARSA p.Gly327Cys Pathogenic same condition
ARSA p.Pro157Arg Pathogenic same condition
ARSA c.1107+1G>A Pathogenic/Likely pathogenic ★★ same type
ARSA c.1107+1G>T Pathogenic ★★ same type
ARSA c.1108-2A>G Pathogenic ★★ same type
ARSA c.1108-3C>G Pathogenic/Likely pathogenic ★★ same type

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/arsa-p-gln488ter (accessed [today's date]).

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