DST p.His1441Arg
c.4322A>G · VCV3600999
Likely pathogenic
No assertion criteria
Classification
Likely pathogenic
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
Conditions
1
multiple sclerosis
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.428 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.9 | GERP 2.9, phastCons 1 |
| Regional constraint | o/e 1.01 | unconstrained · MANE · 36 kb · p 0.7 · regional, not allelic |
| Overall | ||
| CADD | 22.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,708 alleles
Overall
6.84e-05%
1/1,461,318 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
- DST
- Protein
- p.His1441Arg
- Coding
- c.4322A>G
- MANE Select
- NM_001374736
- Type
- single nucleotide variant
- Location
- chr6:56629403 (GRCh38)
- Gene constraint
- LOEUF 0.297 · pLI 1.00 (gnomAD)
Similar variants
- DST p.Leu1441Phe Uncertain significance ★ same residue
- DST p.Leu4500Pro Uncertain significance ★★ same condition
- DST p.Leu5136Val Uncertain significance ★★ same condition
- DST p.Arg9Cys Benign/Likely benign ★★ same condition
- DST p.Lys1270Arg Benign/Likely benign ★★ same condition
- DST p.Glu1112Asp Conflicting classifications of pathogenicity ★ same condition
- DST p.Glu4832Gly Conflicting classifications of pathogenicity ★ same condition
- DST c.22959+1G>A 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/dst-p-his1441arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown