ARSA p.Arg290His
c.869G>A · rs199476355 · VCV68153
Pathogenic/Likely pathogenic
Multiple submitters
Classification
Pathogenic/Likely pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 17 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0329%, mid)
Conditions
2
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.869 | moderately pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.5 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 1.00 | unconstrained · MANE · 2,631 bp · p 0.96 · regional, not allelic |
| Overall | ||
| CADD | 31.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0329%
Middle Eastern · 2/6,084 alleles
Filtering AF
0.0199%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0191%
Overall
0.018%
290/1,613,024 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0329% | 3,042 |
| European (non-Finnish) | 0.0222% | 4,504 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,246 |
| South Asian | 0.00659% | 15,165 |
| African / African-American | 0.00534% | 18,734 |
| Admixed American | 0.005% | 19,993 |
| East Asian | 0.00446% | 22,443 |
| Finnishnot grpmax-eligible | 0.00158% | 63,226 |
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.Arg290His
- Coding
- c.869G>A
- MANE Select
- NM_000487
- dbSNP
- rs199476355
- Type
- single nucleotide variant
- Location
- chr22:50626264 (GRCh38)
- Gene constraint
- LOEUF 1.166 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.43 · 10 PDB
- Residue 290
- an α-helix
Similar variants
- ARSA p.Arg290Cys Pathogenic ★★ same residue
- ARSA p.Arg290Gly Likely pathogenic ★ same residue
- ARSA p.Arg290Pro Likely pathogenic ★ same residue
- ARSA p.Arg290Leu Conflicting classifications of pathogenicity ★ same residue
- ARSA p.Arg290= Likely benign ★ same residue
- ARSA p.Arg290_Met291del Conflicting classifications of pathogenicity ★ same residue
- ARSA c.1107+1G>A Pathogenic/Likely pathogenic ★★ same condition
- ARSA c.1107+1G>T 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-arg290his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown