MITF p.Gln133Ter
c.397C>T · rs2065878986 · VCV872077
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
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 | nonsense (stop-gain) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 3 of 10 |
| Splicing | ||
| SpliceAI | Δ0.34 | donor loss, 17 bp away · masked 0 · deltas |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2.1, phastCons 1 |
| Overall | ||
| CADD | 40.0 | 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
- MITF
- Protein
- p.Gln133Ter
- Coding
- c.397C>T
- MANE Select
- NM_001354604
- dbSNP
- rs2065878986
- Type
- single nucleotide variant
- Location
- chr3:69937864 (GRCh38)
- Gene constraint
- LOEUF 0.482 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.25 · 12 PDB
Similar variants
- MITF p.Gln133Arg Uncertain significance ★ ⚠ same residue
- MITF c.1031+1G>A Pathogenic ★★ same type
- MITF c.1179+1G>A Pathogenic ★★ same type
- MITF c.1180-2A>G Likely pathogenic ★★ same type
- MITF c.355-1062G>C Pathogenic/Likely pathogenic ★★ same type
- MITF c.880+1G>A Likely pathogenic ★★ same type
- MITF c.955+1G>A Likely pathogenic ★★ same type
- MITF c.956-1G>A 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/mitf-p-gln133ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown