ARSA p.His323Pro
c.968A>C · rs545353558 · VCV2301599
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00863%, amr)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.664 | pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>C here scores Δ0.20 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 2.3 | GERP 2, phastCons 1 |
| Regional constraint | o/e 1.00 | unconstrained · MANE · 2,631 bp · p 0.96 · regional, not allelic |
| Overall | ||
| CADD | 23.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00863%
Admixed American · 5/57,966 alleles
Filtering AF
0.00335%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00213%
Overall
0.000311%
5/1,605,226 alleles · very rare
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.His323Pro
- Coding
- c.968A>C
- MANE Select
- NM_000487
- dbSNP
- rs545353558
- Type
- single nucleotide variant
- Location
- chr22:50626165 (GRCh38)
- Gene constraint
- LOEUF 1.166 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.43 · 10 PDB
- Residue 323
- a disulfide bond
Similar variants
- ARSA p.His323Tyr Uncertain significance ★ 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
- ARSA p.Gln373Pro 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-his323pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown