DST p.Ile223Val
c.667A>G · rs546456904 · VCV1754834
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.214%, sas)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.378 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 6.2 | GERP 1.8, phastCons 1 |
| Regional constraint | o/e 0.81 | unconstrained · MANE · 320 kb · p 2.5e-12 · regional, not allelic |
| Overall | ||
| CADD | 22.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.214%
South Asian · 180/83,918 alleles
Filtering AF
0.189%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.179%
Overall
0.0124%
193/1,551,710 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.214% | 466 |
| Remaining individualsnot grpmax-eligible | 0.0183% | 5,471 |
| European (non-Finnish) | 0.000175% | 572,744 |
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.Ile223Val
- Coding
- c.667A>G
- MANE Select
- NM_001374736
- dbSNP
- rs546456904
- Type
- single nucleotide variant
- Location
- chr6:56735248 (GRCh38)
- Gene constraint
- LOEUF 0.297 · pLI 1.00 (gnomAD)
- Residue 223
- the calponin-homology (ch) 2 domain; the 'actin-binding' region
Similar variants
- DST p.Gln4023Ter Pathogenic/Likely pathogenic ★★ same condition
- DST c.16770+5T>C Uncertain significance ★★ same condition
- DST c.17269-3T>A Uncertain significance ★★ same condition
- DST c.18129+3A>G Uncertain significance ★★ same condition
- DST c.182-5C>T Uncertain significance ★★ same condition
- DST c.19896+4C>T Uncertain significance ★★ same condition
- DST c.20551-3A>C Uncertain significance ★★ same condition
- DST c.22959+3A>G 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/dst-p-ile223val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown