Is MITF p.Lys372fs (c.1112_1113dup) pathogenic?

MITF p.Lys372fs (c.11121113dup) is classified Pathogenic in MITF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-31). Associated with Tietz syndrome.

What condition is associated with MITF p.Lys372fs (c.1112_1113dup)?

MITF p.Lys372fs (c.1112_1113dup) is associated with Tietz syndrome, Waardenburg syndrome type 2A, melanoma, cutaneous malignant, susceptibility to, 8 (ClinVar).

MITF p.Lys372fs

c.1112_1113dup · VCV3757480

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Tietz syndrome

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 9 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.3, phastCons 1

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

Variant & gene context

Gene: MITF
Protein: p.Lys372fs
Coding: c.1112_1113dup
MANE Select: NM_001354604
Type: Duplication
Location: chr3:69959352 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.25 · 12 PDB

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

Disease context

Tietz syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Waardenburg syndrome type 2A melanoma, cutaneous malignant, susceptibility to, 8

Similar variants

MITF c.1180-5_1203dup Pathogenic ★ same condition
MITF p.Arg217fs Likely 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
MITF p.Gln365fs Pathogenic ★ same condition
MITF p.His215fs 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-lys372fs (accessed [today's date]).

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