ARSA p.Ala191Val
c.572C>T · rs770694856 · VCV2222406
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0143%, sas)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.237 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.6 | GERP -4.3, phastCons 1 |
| Regional constraint | o/e 1.00 | unconstrained · MANE · 2,631 bp · p 0.96 · regional, not allelic |
| Overall | ||
| CADD | 17.24 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0143%
South Asian · 13/91,086 alleles
Filtering AF
0.00844%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00661%
Overall
0.00144%
21/1,460,740 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0143% | 7,007 |
| European (non-Finnish) | 0.000678% | 147,498 |
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.Ala191Val
- Coding
- c.572C>T
- MANE Select
- NM_000487
- dbSNP
- rs770694856
- Type
- single nucleotide variant
- Location
- chr22:50626946 (GRCh38)
- Gene constraint
- LOEUF 1.166 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.43 · 10 PDB
- Residue 191
- a β-strand; a UniProt-annotated variant site (in mld; juvenile-onset)
Similar variants
- ARSA p.Ala191Thr Uncertain significance ★ same residue
- ARSA p.Ala191= Likely benign ★ same residue
- ARSA p.Arg290His Pathogenic/Likely pathogenic ★★ same condition
- ARSA p.Gly327Ser Pathogenic/Likely pathogenic ★★ same condition
- ARSA p.Pro138Arg Pathogenic/Likely pathogenic ★★ same condition
- ARSA p.Arg216Cys Uncertain significance ★★ same condition
- ARSA p.Arg498Cys Uncertain significance ★★ same condition
- ARSA p.Arg7Leu Uncertain significance ★★ 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-ala191val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown