DST p.Lys1270Arg
c.3809A>G · rs35497571 · VCV357584
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.047 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.9 | GERP 1.3, phastCons 1 |
| Regional constraint | o/e 1.01 | unconstrained · MANE · 36 kb · p 0.7 · regional, not allelic |
| Overall | ||
| CADD | 16.96 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 4.04% | 25 |
| European (non-Finnish)grpmax | 3.17% | 32 |
| Remaining individualsnot grpmax-eligible | 2.42% | 41 |
| South Asian | 1.57% | 64 |
| Ashkenazi Jewishnot grpmax-eligible | 1.3% | 77 |
| Admixed American | 1.15% | 87 |
| Middle Eastern | 0.809% | 124 |
| African / African-American | 0.456% | 219 |
| Amishnot grpmax-eligible | 0.329% | 304 |
| East Asian | 0.0134% | 7,481 |
Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Lys1270Arg
- Coding
- c.3809A>G
- MANE Select
- NM_001374736 · reported on NM_001723
- dbSNP
- rs35497571
- Type
- single nucleotide variant
- Location
- chr6:56620225 (GRCh38)
- Gene constraint
- LOEUF 0.297 · pLI 1.00 (gnomAD)
Disease context
hereditary sensory and autonomic neuropathy type 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: multiple sclerosisepidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency
For Hereditary sensory and autonomic neuropathy type 6 (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
Similar variants
- DST c.22959+1G>A Likely pathogenic ★★ same condition
- DST p.Arg1512Ter Pathogenic/Likely pathogenic ★★ same condition
- DST p.Arg1696Ter Pathogenic/Likely pathogenic ★★ same condition
- DST p.Arg22Ter Likely pathogenic ★★ same condition
- DST p.Arg7329Ter Pathogenic ★★ same condition
- DST p.Cys1828Ter Pathogenic/Likely pathogenic ★★ same condition
- DST p.Gln1124Ter Pathogenic/Likely pathogenic ★★ same condition
- DST p.Gln1366Ter 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/dst-p-lys1270arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown