Is MITF p.Arg324del (c.964AGA[2]) pathogenic?

MITF p.Arg324del (c.964AGA[2]) is classified Pathogenic in MITF (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-08-06). No allele count reported in gnomAD v4.1 (AN 1,612,834); Associated with Monogenic hearing loss.

What condition is associated with MITF p.Arg324del (c.964AGA[2])?

MITF p.Arg324del (c.964AGA[2]) is associated with Monogenic hearing loss, Tietz syndrome, Waardenburg syndrome type 2A (ClinVar).

How common is MITF p.Arg324del (c.964AGA[2]) in the general population?

MITF p.Arg324del (c.964AGA[2]) is no allele count reported in gnomAD v4.1 (AN 1,612,834) (gnomAD).

MITF p.Arg324del

c.964AGA[2] · rs1553704814 · VCV14272

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,834)

Conditions

Monogenic hearing loss

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.3	GERP -2, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,612,834). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MITF
Protein: p.Arg324del
Coding: c.964AGA[2]
MANE Select: NM_001354604
dbSNP: rs1553704814
Type: Microsatellite
Location: chr3:69956461 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.25 · 12 PDB
Residue 324: the bhlh domain; a UniProt-annotated variant site (in commad); a UniProt-annotated variant site (in ws2a and commad; does not localize to the nucleus; does not bind m-box or e-box dna sequences; loss of function in transcriptional regulation; dominant negative effect)

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

Disease context

Monogenic hearing loss

Also linked: Tietz syndrome Waardenburg syndrome type 2A melanoma, cutaneous malignant, susceptibility to, 8 coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness Waardenburg syndrome

Similar variants

MITF p.Arg324Ter Pathogenic ★★ same residue
MITF p.Arg324Lys Pathogenic ★ same residue
MITF p.Arg324Gly Pathogenic same residue
MITF p.Thr299fs Pathogenic ★★ same condition
MITF p.Ser512del Uncertain significance ★★ same condition
MITF p.Ala294fs Likely pathogenic ★ same condition
MITF p.Arg324Thr Likely pathogenic ★ same residue
MITF p.Glu300fs 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-arg324del (accessed [today's date]).

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