MITF p.Thr443fs
c.1327_1328insG · VCV4786390
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
3
melanoma, cutaneous malignant, susceptibility to, 8
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (10 of 10) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 3.3 | GERP -0.15, phastCons 0.97 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- MITF
- Protein
- p.Thr443fs
- Coding
- c.1327_1328insG
- MANE Select
- NM_001354604
- Type
- Insertion
- Location
- chr3:69964994 (GRCh38)
- Gene constraint
- LOEUF 0.482 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.25 · 12 PDB
Disease context
melanoma, cutaneous malignant, susceptibility to, 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: Tietz syndromeWaardenburg syndrome type 2A
For MITF-related melanoma and renal cell carcinoma predisposition syndrome (Orphanet):
- Onset
- Adult, Elderly
Similar variants
- MITF p.Thr443Asn Uncertain significance ★★ ⚠ same residue
- MITF p.Thr443= Likely benign ★★ same residue
- MITF p.Thr293_Ala294insTer Pathogenic ★ same condition
- MITF p.Thr293fs Pathogenic ★ same condition
- MITF p.Thr443Ile Uncertain significance ★ ⚠ same residue
- MITF c.1031+1G>A Pathogenic ★★ same condition
- MITF c.1179+1G>A Pathogenic ★★ same condition
- MITF c.355-1062G>C Pathogenic/Likely pathogenic ★★ 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/mitf-p-thr443fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown