MITF p.Ser236=
c.708T>C · rs1321609968 · VCV2021315
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Conditions
3
Waardenburg syndrome type 2A
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>G here scores Δ0.35 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.7 | GERP 0.92, phastCons 1 |
| Overall | ||
| CADD | 11.78 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,774 alleles
Overall
6.2e-05%
1/1,613,230 alleles · very rare
exomes 1/1,460,980 · genomes 0/152,250 · 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.Ser236=
- Coding
- c.708T>C
- MANE Select
- NM_001354604
- dbSNP
- rs1321609968
- Type
- single nucleotide variant
- Location
- chr3:69941277 (GRCh38)
- Gene constraint
- LOEUF 0.482 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.25 · 12 PDB
- Residue 236
- the 'transactivation' region; an α-helix
Similar variants
- MITF p.Ser236Asn Uncertain significance ★★ ⚠ same residue
- MITF p.Ser236Cys Uncertain significance ★★ ⚠ 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
- MITF c.956-1G>A 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-ser236 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown