Is MITF p.Lys379Ter (c.1135A>T) pathogenic?

MITF p.Lys379Ter (c.1135A>T) is classified Likely pathogenic in MITF (ClinVar, No assertion criteria, 1 submitter; last evaluated 2026-04-23). Absent from gnomAD v4.1; Associated with coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness.

What condition is associated with MITF p.Lys379Ter (c.1135A>T)?

MITF p.Lys379Ter (c.1135A>T) is associated with coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness (ClinVar).

How common is MITF p.Lys379Ter (c.1135A>T) in the general population?

MITF p.Lys379Ter (c.1135A>T) is absent from gnomAD v4.1 (gnomAD).

MITF p.Lys379Ter

c.1135A>T · VCV4871873

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (9 of 10, 44 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Overall
CADD	42.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MITF
Protein: p.Lys379Ter
Coding: c.1135A>T
MANE Select: NM_001354604
Type: single nucleotide variant
Location: chr3:69959376 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.25 · 12 PDB
Residue 379: the 'leucine-zipper' region; an α-helix

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

Disease context

coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MITF p.Lys379= Likely benign ★★ same residue
MITF p.Lys379Asn Uncertain significance ★ ⚠ same residue
MITF p.Lys379Glu Uncertain significance ★ ⚠ same residue
MITF c.956-1G>A Pathogenic ★★ same condition
MITF c.881-9C>G Uncertain significance ★★ same condition
MITF p.Ala294Val Uncertain significance ★★ ⚠ same condition
MITF p.Ala384Ser Uncertain significance ★★ ⚠ same condition
MITF p.Arg420Gln 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-lys379ter (accessed [today's date]).

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