Is MITF p.Val473Ile (c.1417G>A) pathogenic?

MITF p.Val473Ile (c.1417G>A) is classified Uncertain significance in MITF (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-17). AlphaMissense: likely benign (0.0662); Absent from gnomAD v4.1.

How common is MITF p.Val473Ile (c.1417G>A) in the general population?

MITF p.Val473Ile (c.1417G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MITF p.Val473Ile (c.1417G>A)?

AlphaMissense predicts likely benign (score 0.0662) — an in-silico prediction, not a clinical call.

MITF p.Val473Ile

c.1417G>A · rs2107552828 · VCV1313653

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0662 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0662	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -6.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP -1.7, phastCons 0.75
Regional constraint	o/e 1.07	unconstrained · MANE · 5,907 bp · p 0.32 · regional, not allelic
Overall
CADD	12.45	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Val473Ile
Coding: c.1417G>A
MANE Select: NM_001354604
dbSNP: rs2107552828
Type: single nucleotide variant
Location: chr3:69965084 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.25 · 12 PDB

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

Similar variants

MITF p.Val473= Likely benign ★ same residue
MITF c.1031+1G>A Pathogenic ★★ same type
MITF c.1179+1G>A Pathogenic ★★ same type
MITF c.1180-2A>G Likely pathogenic ★★ same type
MITF c.355-1062G>C Pathogenic/Likely pathogenic ★★ same type
MITF c.880+1G>A Likely pathogenic ★★ same type
MITF c.955+1G>A Likely pathogenic ★★ same type
MITF c.956-1G>A Pathogenic ★★ same type

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-val473ile (accessed [today's date]).

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