DST p.Ile248Val
c.742A>G · rs112635185 · VCV871263
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.199%, nfe)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.669 | pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.9 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 0.81 | unconstrained · MANE · 320 kb · p 2.5e-12 · regional, not allelic |
| Overall | ||
| CADD | 21.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.199%
European (non-Finnish) · 2,307/1,157,926 alleles
Filtering AF
0.192%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.19%
Overall
0.166%
2,607/1,572,826 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.199% | 502 |
| Remaining individualsnot grpmax-eligible | 0.151% | 663 |
| South Asian | 0.145% | 691 |
| Admixed American | 0.0778% | 1,285 |
| African / African-American | 0.0353% | 2,831 |
| Middle Eastern | 0.0334% | 2,990 |
| Finnishnot grpmax-eligible | 0.0224% | 4,460 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00347% | 28,802 |
| East Asian | 0.00228% | 43,850 |
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.Ile248Val
- Coding
- c.742A>G
- MANE Select
- NM_001374736
- dbSNP
- rs112635185
- Type
- single nucleotide variant
- Location
- chr6:56704315 (GRCh38)
- Gene constraint
- LOEUF 0.297 · pLI 1.00 (gnomAD)
- Residue 248
- 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-ile248val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown