Is MITF p.Arg217fs (c.648dup) pathogenic?

MITF p.Arg217fs (c.648dup) is classified Likely pathogenic in MITF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). Associated with Waardenburg syndrome type 2A.

What condition is associated with MITF p.Arg217fs (c.648dup)?

MITF p.Arg217fs (c.648dup) is associated with Waardenburg syndrome type 2A (ClinVar).

MITF p.Arg217fs

c.648dup · VCV3601239

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Waardenburg syndrome type 2A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: MITF
Protein: p.Arg217fs
Coding: c.648dup
MANE Select: NM_001354604
Type: Duplication
Location: chr3:69939162 (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

Full MITF gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Waardenburg syndrome type 2A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MITF p.Arg217Ter Pathogenic/Likely pathogenic ★★ same residue
MITF p.Arg217Gln Uncertain significance ★★ ⚠ same residue
MITF p.Arg217= Likely benign ★★ same residue
MITF c.1180-5_1203dup Pathogenic ★ same condition
MITF p.Arg400Ter Pathogenic ★ same condition
MITF p.Asn430fs Pathogenic ★ same condition
MITF p.Cys431fs Pathogenic ★ same condition
MITF p.Gln132fs 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-arg217fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown