Is MITF p.Arg310= (c.930G>A) pathogenic?

MITF p.Arg310= (c.930G>A) is classified Likely benign in MITF (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-15). Very rare (popmax 0.00134%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with MITF p.Arg310= (c.930G>A)?

MITF p.Arg310= (c.930G>A) is associated with hereditary neoplastic syndrome, Tietz syndrome, Waardenburg syndrome type 2A (ClinVar).

How common is MITF p.Arg310= (c.930G>A) in the general population?

MITF p.Arg310= (c.930G>A) is very rare (popmax 0.00134%, afr) (gnomAD).

MITF p.Arg310=

c.930G>A · rs755901867 · VCV1204089

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

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 1.4	GERP 0.33, phastCons 1
Overall
CADD	7.78	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,870 alleles

Overall 0.000124% 2/1,613,138 alleles · very rare exomes 1/1,461,084 · genomes 1/152,054 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,870
South Asian	0.0011%	91,080

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MITF
Protein: p.Arg310=
Coding: c.930G>A
MANE Select: NM_001354604
dbSNP: rs755901867
Type: single nucleotide variant
Location: chr3:69951861 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.25 · 12 PDB
Residue 310: a UniProt-annotated variant site (in ws2a; uncertain significance)

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.Arg310Gly Likely pathogenic ★★ same residue
MITF p.Arg310Lys Uncertain significance ★ ⚠ same residue
MITF p.Arg310Ser 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-arg310 (accessed [today's date]).

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