ARSA p.Glu331Lys
c.991G>A · rs398123419 · VCV556001
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00457%, sas)
Conditions
2
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.84 | moderately pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 4.8 | GERP 2.2, phastCons 1 |
| Regional constraint | o/e 1.00 | unconstrained · MANE · 2,631 bp · p 0.96 · regional, not allelic |
| Overall | ||
| CADD | 25.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00457%
South Asian · 4/87,442 alleles
Filtering AF
0.00147%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00092%
Overall
0.00138%
22/1,592,846 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00457% | 21,861 |
| Admixed American | 0.00183% | 54,780 |
| European (non-Finnish) | 0.00145% | 68,938 |
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.Glu331Lys
- Coding
- c.991G>A
- MANE Select
- NM_000487
- dbSNP
- rs398123419
- Type
- single nucleotide variant
- Location
- chr22:50626052 (GRCh38)
- Gene constraint
- LOEUF 1.166 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.43 · 10 PDB
- Residue 331
- a disulfide bond
Similar variants
- ARSA p.Glu331Ter Pathogenic/Likely pathogenic ★★ same residue
- ARSA p.Glu331Gly Likely pathogenic ★ 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
- ARSA c.224+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/arsa-p-glu331lys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown