DUSP6 c.838+3G>C
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0496%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +3 | donor splice region (+3, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Pangolin | Δ0.48 | loss · gain 0.01 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 6 | GERP 2.2, phastCons 1 |
| Non-coding constraint | Z 0.76 | 1 kb window · o/e 0.94 · regional · uncalibrated |
| Overall | ||
| CADD | 22.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0496%
Middle Eastern · 3/6,050 alleles
Filtering AF
0.0141%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0134%
Overall
0.0129%
208/1,611,834 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0496% | 2,017 |
| European (non-Finnish) | 0.016% | 6,236 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,936 |
| Admixed American | 0.00834% | 11,991 |
| African / African-American | 0.00267% | 37,471 |
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
- DUSP6
- Coding
- c.838+3G>C
- MANE Select
- NM_001946
- dbSNP
- rs371728439
- Type
- single nucleotide variant
- Location
- chr12:89350585 (GRCh38)
- Gene constraint
- LOEUF 0.45 · pLI 0.99 (gnomAD)
- Structure
- AlphaFold pLDDT 76.13 · 2 PDB
Similar variants
- DUSP6 p.Ala141Asp Uncertain significance ★★ ⚠ same type
- DUSP6 p.Ala57Thr Uncertain significance ★★ ⚠ same type
- DUSP6 p.Asp93Glu Uncertain significance ★★ ⚠ same type
- DUSP6 p.Glu32Lys Uncertain significance ★★ ⚠ same type
- DUSP6 p.Gly30Cys Uncertain significance ★★ ⚠ same type
- DUSP6 p.Phe77Ile Uncertain significance ★★ ⚠ same type
- DUSP6 c.400+231T>C Benign ★★ same type
- DUSP6 c.401-113T>A Benign ★★ 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/dusp6-c-838-plus-3g-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown