ARSA p.Gly124Ser
c.370G>A · rs74315461 · VCV3063
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 10 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00226%, eas)
Conditions
2
ARSA-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.922 | moderately pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.40 | donor loss · deltas |
| Constraint at this position | ||
| Conservation | phyloP 5.9 | GERP 0.96, phastCons 1 |
| Regional constraint | o/e 1.00 | unconstrained · MANE · 2,631 bp · p 0.96 · regional, not allelic |
| Overall | ||
| CADD | 27.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00226%
East Asian · 1/44,260 alleles
Filtering AF
0.000545%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00043%
Overall
0.000999%
16/1,601,472 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00226% | 44,260 |
| South Asian | 0.00223% | 44,920 |
| African / African-American | 0.00134% | 74,670 |
| European (non-Finnish) | 0.00102% | 97,903 |
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.Gly124Ser
- Coding
- c.370G>A
- MANE Select
- NM_000487
- dbSNP
- rs74315461
- Type
- single nucleotide variant
- Location
- chr22:50627261 (GRCh38)
- Gene constraint
- LOEUF 1.166 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.43 · 10 PDB
Similar variants
- ARSA p.Gly124Asp Pathogenic/Likely pathogenic ★★ same residue
- ARSA p.Gly124Cys Likely pathogenic ★ same residue
- ARSA p.Gly124_Lys125delinsThrLeuGly Conflicting classifications of pathogenicity ★ same residue
- ARSA p.Gly124Arg Uncertain significance ★ 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
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-gly124ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown