Is MITF p.Arg513= (c.1537C>A) pathogenic?

MITF p.Arg513= (c.1537C>A) is classified Likely benign in MITF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-31). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with MITF p.Arg513= (c.1537C>A)?

MITF p.Arg513= (c.1537C>A) is associated with hereditary neoplastic syndrome, Tietz syndrome, Waardenburg syndrome type 2A (ClinVar).

How common is MITF p.Arg513= (c.1537C>A) in the general population?

MITF p.Arg513= (c.1537C>A) is absent from gnomAD v4.1 (gnomAD).

MITF p.Arg513=

c.1537C>A · rs752915964 · VCV1998719

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 3.4	GERP 0.28, phastCons 1
Overall
CADD	9.896	PHRED · no single calibrated threshold — expert panels disagree

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.Arg513=
Coding: c.1537C>A
MANE Select: NM_001354604
dbSNP: rs752915964
Type: single nucleotide variant
Location: chr3:69965204 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.25 · 12 PDB
Residue 513: the 'disordered' region

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

Also linked: Tietz syndrome Waardenburg syndrome type 2A melanoma, cutaneous malignant, susceptibility to, 8

Similar variants

MITF p.Arg513Gln Uncertain significance ★★ ⚠ same residue
MITF p.Arg513Gly Uncertain significance ★ same residue
MITF p.Arg513Trp Uncertain significance ★ same residue
MITF c.1031+1G>A Pathogenic ★★ same condition
MITF c.1179+1G>A Pathogenic ★★ same condition
MITF c.355-1062G>C Pathogenic/Likely pathogenic ★★ same condition
MITF c.880+1G>A Likely pathogenic ★★ same condition
MITF c.955+1G>A 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-arg513 (accessed [today's date]).

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