ARSA p.Ser227Cys
c.680C>G · rs138468395 · VCV1436820
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.056%, afr)
Conditions
2
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.864 | moderately pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.2, phastCons 1 |
| Regional constraint | o/e 1.00 | unconstrained · MANE · 2,631 bp · p 0.96 · regional, not allelic |
| Overall | ||
| CADD | 26.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.056%
African / African-American · 42/75,032 alleles
Filtering AF
0.0425%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0378%
Overall
0.0026%
42/1,612,718 alleles · ultra-rare
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
- ARSA
- Protein
- p.Ser227Cys
- Coding
- c.680C>G
- MANE Select
- NM_000487
- dbSNP
- rs138468395
- Type
- single nucleotide variant
- Location
- chr22:50626838 (GRCh38)
- Gene constraint
- LOEUF 1.166 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.43 · 10 PDB
- Residue 227
- a UniProt-annotated variant site (in mld; late-infantile form)
Similar variants
- ARSA p.Ser227Phe Likely pathogenic ★ same residue
- ARSA p.Ser227Pro Likely pathogenic ★ same residue
- ARSA p.Ser227= Likely benign ★ same residue
- ARSA c.1107+1G>A Pathogenic/Likely pathogenic ★★ same condition
- ARSA c.1107+1G>T Pathogenic ★★ same condition
- ARSA c.1108-2A>G Pathogenic ★★ same condition
- ARSA c.1108-3C>G Pathogenic/Likely pathogenic ★★ same condition
- ARSA c.1210+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/arsa-p-ser227cys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown