MITF p.Leu406=
c.1218T>C · VCV4108314
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
1
hereditary neoplastic syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.8 | GERP -4.3 |
| Overall | ||
| CADD | 1.209 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,020 alleles
Overall
6.2e-05%
1/1,614,160 alleles · very rare
exomes 1/1,461,866 · genomes 0/152,294 · joint denominator
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
- MITF
- Protein
- p.Leu406=
- Coding
- c.1218T>C
- MANE Select
- NM_001354604
- Type
- single nucleotide variant
- Location
- chr3:69964885 (GRCh38)
- Gene constraint
- LOEUF 0.482 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.25 · 12 PDB
- Residue 406
- the 'dna-binding regulation' region
Similar variants
- MITF p.Leu406Phe Uncertain significance ★★ ⚠ same residue
- MITF p.Arg362Ter Pathogenic/Likely pathogenic ★★ same condition
- MITF c.881-9C>G Uncertain significance ★★ same condition
- MITF p.Ala148Thr Uncertain significance ★★ ⚠ same condition
- MITF p.Ala152Thr Uncertain significance ★★ ⚠ same condition
- MITF p.Ala177Thr Uncertain significance ★★ ⚠ same condition
- MITF p.Ala183Ser Uncertain significance ★★ ⚠ same condition
- MITF p.Ala205Thr 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-leu406 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown