Is MITF p.Gln378= (c.1134G>A) pathogenic?

MITF p.Gln378= (c.1134G>A) is classified Likely benign in MITF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-08). Very rare (popmax 8.48e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with MITF p.Gln378= (c.1134G>A)?

MITF p.Gln378= (c.1134G>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is MITF p.Gln378= (c.1134G>A) in the general population?

MITF p.Gln378= (c.1134G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

MITF p.Gln378=

c.1134G>A · VCV3873262

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

hereditary neoplastic syndrome

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 5.9	GERP 1.3, phastCons 1
Overall
CADD	9.632	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,906 alleles

Overall 6.84e-05% 1/1,461,666 alleles · very rare

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.Gln378=
Coding: c.1134G>A
MANE Select: NM_001354604
Type: single nucleotide variant
Location: chr3:69959375 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.25 · 12 PDB
Residue 378: the 'leucine-zipper' region; an α-helix

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

Disease context

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

Similar variants

MITF p.Gln378Arg Uncertain significance ★ ⚠ same residue
MITF p.Gln378Ter Pathogenic ★ same residue
MITF p.Gln378His Uncertain significance ★ ⚠ same residue
MITF p.Arg362Ter Pathogenic/Likely pathogenic ★★ same condition
MITF c.881-9C>G Uncertain significance ★★ same condition
MITF p.Ala148Thr Uncertain significance ★★ ⚠ same condition
MITF p.Ala152Thr Uncertain significance ★★ ⚠ same condition
MITF p.Ala177Thr Uncertain significance ★★ ⚠ 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-gln378 (accessed [today's date]).

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