MITF p.Ala82=
c.246G>A · rs542555095 · VCV678627
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.224%, sas)
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 | GERP -5.2 |
| Overall | ||
| CADD | 7.954 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.224%
South Asian · 204/91,080 alleles
Filtering AF
0.199%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.189%
Overall
0.0144%
233/1,614,182 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.224% | 446 |
| Middle Eastern | 0.033% | 3,031 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,418 |
| East Asian | 0.00891% | 11,218 |
| African / African-American | 0.00267% | 37,522 |
| European (non-Finnish) | 0.00127% | 78,670 |
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.Ala82=
- Coding
- c.246G>A
- MANE Select
- NM_001354604
- dbSNP
- rs542555095
- Type
- single nucleotide variant
- Location
- chr3:69879275 (GRCh38)
- Gene constraint
- LOEUF 0.482 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.25 · 12 PDB
Similar variants
- 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
- MITF p.Arg217Ter Pathogenic/Likely 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-ala82 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown