Is MITF p.Pro210Arg (c.629C>G) pathogenic?

MITF p.Pro210Arg (c.629C>G) is classified Uncertain significance in MITF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-11). AlphaMissense: likely benign (0.091); Absent from gnomAD v4.1; Associated with Waardenburg syndrome type 2A.

What condition is associated with MITF p.Pro210Arg (c.629C>G)?

MITF p.Pro210Arg (c.629C>G) is associated with Waardenburg syndrome type 2A, Tietz syndrome, melanoma, cutaneous malignant, susceptibility to, 8 (ClinVar).

How common is MITF p.Pro210Arg (c.629C>G) in the general population?

MITF p.Pro210Arg (c.629C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MITF p.Pro210Arg (c.629C>G)?

AlphaMissense predicts likely benign (score 0.091) — an in-silico prediction, not a clinical call.

MITF p.Pro210Arg

c.629C>G · VCV3754852

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.091 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Waardenburg syndrome type 2A

Computational evidence

Protein change
AlphaMissense	0.091	likely benign
REVEL	0.124	moderately benign-leaning
SaProt	LLR -7.11	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 6	GERP 2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 14 kb · p 0.51 · regional, not allelic
Overall
CADD	22.7	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.Pro210Arg
Coding: c.629C>G
MANE Select: NM_001354604
Type: single nucleotide variant
Location: chr3:69939144 (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

Disease context

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

Also linked: Tietz syndrome melanoma, cutaneous malignant, susceptibility to, 8

Similar variants

MITF p.Pro210Gln Uncertain significance ★ ⚠ same residue
MITF p.Pro210Leu Uncertain significance ★ ⚠ same residue
MITF p.Pro210= Likely benign ★ 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-pro210arg (accessed [today's date]).

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