Is MITF p.Pro164fs (c.491del) pathogenic?

MITF p.Pro164fs (c.491del) is classified Pathogenic in MITF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-04). Associated with melanoma, cutaneous malignant, susceptibility to, 8.

What condition is associated with MITF p.Pro164fs (c.491del)?

MITF p.Pro164fs (c.491del) is associated with melanoma, cutaneous malignant, susceptibility to, 8, Tietz syndrome, Waardenburg syndrome type 2A (ClinVar).

MITF p.Pro164fs

c.491del · VCV3757969

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

melanoma, cutaneous malignant, susceptibility to, 8

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 3 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.6	GERP 1.2, phastCons 1

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

Variant & gene context

Gene: MITF
Protein: p.Pro164fs
Coding: c.491del
MANE Select: NM_001354604
Type: Deletion
Location: chr3:69937957 (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

melanoma, cutaneous malignant, susceptibility to, 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Tietz syndrome Waardenburg syndrome type 2A

For MITF-related melanoma and renal cell carcinoma predisposition syndrome (Orphanet):

Onset: Adult, Elderly

Similar variants

MITF p.Pro164Ser Uncertain significance ★★ ⚠ same residue
MITF p.Asp225fs Pathogenic ★★ same condition
MITF p.Pro272fs Pathogenic ★★ same condition
MITF c.660_666+6del Likely pathogenic ★ same condition
MITF c.880+1del Pathogenic ★ same condition
MITF c.953_955+3del Likely pathogenic ★ same condition
MITF p.Ala305fs Pathogenic ★ same condition
MITF p.Ala399fs 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-pro164fs (accessed [today's date]).

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