DST p.Leu251=
c.751T>C · rs16888128 · VCV1278369
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 32.7%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 4.8 | GERP -3.6, phastCons 1 |
| Overall | ||
| CADD | 8.256 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
32.7%
African / African-American · 23,837/72,930 alleles
Filtering AF
32.3%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 32.2%
Overall
20.6%
320,949/1,554,446 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 32.7% | 3 |
| European (non-Finnish) | 22.3% | 4 |
| Middle Eastern | 22% | 5 |
| Amishnot grpmax-eligible | 21.2% | 5 |
| Remaining individualsnot grpmax-eligible | 19.9% | 5 |
| Finnishnot grpmax-eligible | 17.7% | 6 |
| Ashkenazi Jewishnot grpmax-eligible | 14.7% | 7 |
| Admixed American | 12.3% | 8 |
| South Asian | 7.03% | 14 |
| East Asian | 1.54% | 65 |
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.Leu251=
- Coding
- c.751T>C
- MANE Select
- NM_001374736
- dbSNP
- rs16888128
- Type
- single nucleotide variant
- Location
- chr6:56704306 (GRCh38)
- Gene constraint
- LOEUF 0.297 · pLI 1.00 (gnomAD)
- Residue 251
- the calponin-homology (ch) 2 domain; the 'actin-binding' region
Similar variants
- DST c.22959+1G>A Likely pathogenic ★★ same type
- DST p.Arg1512Ter Pathogenic/Likely pathogenic ★★ same type
- DST p.Arg1696Ter Pathogenic/Likely pathogenic ★★ same type
- DST p.Arg22Ter Likely pathogenic ★★ same type
- DST p.Arg7329Ter Pathogenic ★★ same type
- DST p.Cys1828Ter Pathogenic/Likely pathogenic ★★ same type
- DST p.Gln1124Ter Pathogenic/Likely pathogenic ★★ same type
- DST p.Gln1366Ter Pathogenic/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-leu251 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown