MITF p.Arg217=
c.651A>C · rs1315093654 · VCV2941060
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000186%)
Conditions
4
Tietz 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 1.1 | GERP -2.3, phastCons 0.91 |
| Overall | ||
| CADD | 8.169 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000186%
Overall
0.000186%
3/1,614,084 alleles · very rare
exomes 3/1,461,744 · genomes 0/152,340 · 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.Arg217=
- Coding
- c.651A>C
- MANE Select
- NM_001354604
- dbSNP
- rs1315093654
- Type
- single nucleotide variant
- Location
- chr3:69939166 (GRCh38)
- Gene constraint
- LOEUF 0.482 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.25 · 12 PDB
- Residue 217
- an α-helix
Similar variants
- MITF p.Arg217Ter Pathogenic/Likely pathogenic ★★ same residue
- MITF p.Arg217Gln Uncertain significance ★★ ⚠ same residue
- MITF p.Arg217fs Likely pathogenic ★ 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
- MITF c.880+1G>A Likely pathogenic ★★ same condition
- MITF c.955+1G>A 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-arg217 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown