Is MITF p.Arg323fs (c.967del) pathogenic?

MITF p.Arg323fs (c.967del) is classified Pathogenic in MITF (ClinVar, Single submitter, 2 submitters; last evaluated 2019-01-01). No gnomAD frequency available for this variant; Associated with Waardenburg syndrome type 2A.

What condition is associated with MITF p.Arg323fs (c.967del)?

MITF p.Arg323fs (c.967del) is associated with Waardenburg syndrome type 2A (ClinVar).

How common is MITF p.Arg323fs (c.967del) in the general population?

MITF p.Arg323fs (c.967del) is no gnomAD frequency available for this variant (gnomAD).

MITF p.Arg323fs

c.967del · rs2066400236 · VCV995919

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Waardenburg syndrome type 2A

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 8 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Arg323fs
Coding: c.967del
MANE Select: NM_001354604
dbSNP: rs2066400236
Type: Deletion
Location: chr3:69956465 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.25 · 12 PDB
Residue 323: the bhlh domain

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

Disease context

Waardenburg syndrome type 2A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MITF p.Arg323Gly Conflicting classifications of pathogenicity ★ ⚠ 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-arg323fs (accessed [today's date]).

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