ARSA p.Pro73Leu
c.218C>T · rs764004751 · VCV2503923
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00238%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.938 | strongly 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 | 32.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00238%
East Asian · 1/42,008 alleles
Filtering AF
0.000822%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000665%
Overall
0.00122%
19/1,560,548 alleles · very rare
exomes 18/1,408,526 · genomes 1/152,022 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00238% | 42,008 |
| European (non-Finnish) | 0.00139% | 71,996 |
| African / African-American | 0.00136% | 73,600 |
| South Asian | 0.00117% | 85,268 |
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.Pro73Leu
- Coding
- c.218C>T
- MANE Select
- NM_000487
- dbSNP
- rs764004751
- Type
- single nucleotide variant
- Location
- chr22:50627562 (GRCh38)
- Gene constraint
- LOEUF 1.166 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.43 · 10 PDB
- Residue 73
- an α-helix
Similar variants
- ARSA p.Pro73Ser Uncertain significance ★★ same residue
- ARSA c.1107+1G>A Pathogenic/Likely pathogenic ★★ same type
- ARSA c.1107+1G>T Pathogenic ★★ same type
- ARSA c.1108-2A>G Pathogenic ★★ same type
- ARSA c.1108-3C>G Pathogenic/Likely pathogenic ★★ same type
- ARSA c.1210+1G>A Pathogenic ★★ same type
- ARSA c.224+1G>A Likely pathogenic ★★ same type
- ARSA c.225-1G>C Likely pathogenic ★★ 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/arsa-p-pro73leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown