ARSK p.Ser430=
c.1290G>A · VCV4853321
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 2.84%, afr)
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 -3.5 | GERP -3.9 |
| Overall | ||
| CADD | 0.852 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.84%
African / African-American · 2,130/74,996 alleles
Filtering AF
2.74%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.7%
Overall
0.148%
2,394/1,613,844 alleles · low-frequency
exomes 1,177/1,461,634 · genomes 1,217/152,210 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.84% | 35 |
| Remaining individualsnot grpmax-eligible | 0.205% | 488 |
| Admixed American | 0.17% | 588 |
| Middle Eastern | 0.099% | 1,010 |
| South Asian | 0.011% | 9,106 |
| European (non-Finnish) | 0.00153% | 65,546 |
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
- ARSK
- Protein
- p.Ser430=
- Coding
- c.1290G>A
- MANE Select
- NM_198150
- Type
- single nucleotide variant
- Location
- chr5:95601040 (GRCh38)
- Gene constraint
- LOEUF 0.954 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.50
- Residue 430
- a UniProt-annotated variant site (in mps10; mutant protein is not detected by western blot in transfected cells; severely decreased glucuronate-2-sulfatase activity)
Similar variants
- ARSK p.Ser430Leu Uncertain significance ★ ⚠ same residue
- ARSK p.Lys518= Benign/Likely benign ★★ same type
- ARSK p.Ala11Thr Uncertain significance ★ ⚠ same type
- ARSK p.Ala191Pro Uncertain significance ★ ⚠ same type
- ARSK p.Ala238Asp Uncertain significance ★ ⚠ same type
- ARSK p.Ala318Thr Uncertain significance ★ ⚠ same type
- ARSK p.Ala428Gly Uncertain significance ★ ⚠ same type
- ARSK p.Arg122Gln Uncertain significance ★ ⚠ 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/arsk-p-ser430 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown