DST p.Val99Met
c.295G>A · rs11969595 · VCV1229366
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 10.4%, 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. | ||
| REVEL | 0.18 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.29 | GERP -1.8 |
| Regional constraint | o/e 0.81 | unconstrained · MANE · 320 kb · p 2.5e-12 · regional, not allelic |
| Overall | ||
| CADD | 15.39 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
10.4%
African / African-American · 7,076/67,796 alleles
Filtering AF
10.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 10.2%
Overall
0.621%
8,495/1,367,610 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 10.4% | 10 |
| Admixed American | 0.806% | 124 |
| Remaining individualsnot grpmax-eligible | 0.657% | 152 |
| Middle Eastern | 0.503% | 199 |
| European (non-Finnish) | 0.0631% | 1,584 |
| South Asian | 0.025% | 4,002 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00491% | 20,366 |
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.Val99Met
- Coding
- c.295G>A
- MANE Select
- NM_001374736
- dbSNP
- rs11969595
- Type
- single nucleotide variant
- Location
- chr6:56900543 (GRCh38)
- Gene constraint
- LOEUF 0.297 · pLI 1.00 (gnomAD)
- Residue 99
- the calponin-homology (ch) 1 domain; the 'actin-binding' region
Similar variants
- DST p.Val99Leu Uncertain significance ★ same residue
- 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
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-val99met (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown