Is MITF p.Val226= (c.678A>C) pathogenic?

MITF p.Val226= (c.678A>C) is classified Likely benign in MITF (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-10). No allele count reported in gnomAD v4.1 (AN 1,606,118); Associated with hereditary neoplastic syndrome.

What condition is associated with MITF p.Val226= (c.678A>C)?

MITF p.Val226= (c.678A>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is MITF p.Val226= (c.678A>C) in the general population?

MITF p.Val226= (c.678A>C) is no allele count reported in gnomAD v4.1 (AN 1,606,118) (gnomAD).

MITF p.Val226=

c.678A>C · VCV4860057

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,606,118)

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 0.81	GERP -3.4, phastCons 0.99
Overall
CADD	3.764	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,606,118). 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.Val226=
Coding: c.678A>C
MANE Select: NM_001354604
Type: single nucleotide variant
Location: chr3:69941247 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.25 · 12 PDB
Residue 226: the 'transactivation' region; an α-helix

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

Similar variants

MITF p.Val226Glu Uncertain significance ★ ⚠ same residue
MITF p.Arg362Ter Pathogenic/Likely pathogenic ★★ same condition
MITF c.881-9C>G Uncertain significance ★★ same condition
MITF p.Ala148Thr Uncertain significance ★★ ⚠ same condition
MITF p.Ala152Thr Uncertain significance ★★ ⚠ same condition
MITF p.Ala177Thr Uncertain significance ★★ ⚠ same condition
MITF p.Ala183Ser Uncertain significance ★★ ⚠ same condition
MITF p.Ala205Thr 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-val226 (accessed [today's date]).

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