DES c.735+2T>C
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
canonical splice-site (±1/±2)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | canonical splice-site (±1/±2) | predicted loss-of-function |
|---|---|---|
| Splicing | ||
| Splice region | donor +2 | canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone |
| SpliceAI | Δ0.98 | donor loss · deltas |
| Pangolin | Δ0.87 | loss · gain 0.27 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.8 | GERP 1.9, phastCons 1 |
| Non-coding constraint | Z 6.04 | 1 kb window · o/e 0.63 · regional · uncalibrated |
| Overall | ||
| CADD | 33.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- DES
- Coding
- c.735+2T>C
- MANE Select
- NM_001927
- dbSNP
- rs949187421
- Type
- single nucleotide variant
- Location
- chr2:219420348 (GRCh38)
- Gene constraint
- LOEUF 0.81 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.73
Similar variants
- DES c.1289-2A>G Pathogenic/Likely pathogenic ★★ same type
- DES c.579-2A>C Likely pathogenic ★★ same type
- DES c.735+1G>A Pathogenic/Likely pathogenic ★★ same type
- DES c.735+1G>C Pathogenic/Likely pathogenic ★★ same type
- DES c.735+3A>G Pathogenic ★★ same type
- DES c.736-1G>A Likely pathogenic ★★ same type
- DES p.Ala120Pro Pathogenic/Likely pathogenic ★★ same type
- DES p.Ala285Val 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/des-c-735-plus-2t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown