MITF p.Leu381fs
c.1142_1143del · VCV4529479
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
Monogenic hearing loss
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 within the last 50 nt of the penultimate exon (9 of 10, 37 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 1.8 | GERP 0.43, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- MITF
- Protein
- p.Leu381fs
- Coding
- c.1142_1143del
- MANE Select
- NM_001354604
- Type
- Deletion
- Location
- chr3:69959383 (GRCh38)
- Gene constraint
- LOEUF 0.482 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.25 · 12 PDB
- Residue 381
- the 'leucine-zipper' region; an α-helix
Disease context
Monogenic hearing loss
Similar variants
- MITF p.Asp263fs Likely pathogenic ★ same condition
- MITF p.His316del Likely pathogenic ★ same condition
- MITF p.Asn279fs Likely pathogenic same condition
- MITF p.Arg321Ter Pathogenic ★★ same condition
- MITF p.Arg324del Pathogenic ★★ same condition
- MITF p.Gly351Glu Likely pathogenic ★★ same condition
- MITF p.Cys295Tyr Uncertain significance ★★ ⚠ same condition
- MITF p.Gly174Arg 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/mitf-p-leu381fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown