Is MITF p.Ser512del (c.1531AGC[1]) pathogenic?

MITF p.Ser512del (c.1531AGC[1]) is classified Uncertain significance in MITF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-30). Absent from gnomAD; Associated with melanoma, cutaneous malignant, susceptibility to, 8.

What condition is associated with MITF p.Ser512del (c.1531AGC[1])?

MITF p.Ser512del (c.1531AGC[1]) is associated with melanoma, cutaneous malignant, susceptibility to, 8, Tietz syndrome, Waardenburg syndrome type 2A (ClinVar).

How common is MITF p.Ser512del (c.1531AGC[1]) in the general population?

MITF p.Ser512del (c.1531AGC[1]) is absent from gnomAD (gnomAD).

MITF p.Ser512del

c.1531AGC[1] · rs1576071470 · VCV809507

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

melanoma, cutaneous malignant, susceptibility to, 8

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 -4.8	GERP -4.3

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.Ser512del
Coding: c.1531AGC[1]
MANE Select: NM_001354604
dbSNP: rs1576071470
Type: Microsatellite
Location: chr3:69965198 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.25 · 12 PDB
Residue 512: the 'disordered' region

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

Disease context

melanoma, cutaneous malignant, susceptibility to, 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Tietz syndrome Waardenburg syndrome type 2A

For MITF-related melanoma and renal cell carcinoma predisposition syndrome (Orphanet):

Onset: Adult, Elderly

Similar variants

MITF p.Arg324del Pathogenic ★★ same condition
MITF p.Thr299fs Pathogenic ★★ same condition
MITF p.Ala294fs Likely pathogenic ★ same condition
MITF p.Glu300fs Likely pathogenic ★ same condition
MITF p.Ser216fs Pathogenic ★ same condition
MITF p.Ser258fs Pathogenic ★ same condition
MITF p.Leu436_Gln437insLeu Uncertain significance ★ same condition
MITF p.Ser512= Conflicting classifications of pathogenicity ★ same residue

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-ser512del (accessed [today's date]).

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