Is MITF p.Thr110= (c.330G>A) pathogenic?

MITF p.Thr110= (c.330G>A) is classified Benign in MITF (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-03-04). Common (popmax 5.52%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Waardenburg syndrome type 2A.

What condition is associated with MITF p.Thr110= (c.330G>A)?

MITF p.Thr110= (c.330G>A) is associated with Waardenburg syndrome type 2A, melanoma, cutaneous malignant, susceptibility to, 8 (ClinVar).

MITF p.Thr110=

Q: How common is MITF p.Thr110= (c.330G>A) in the general population?

MITF p.Thr110= (c.330G>A) is common (popmax 5.52%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.330G>A · rs9849776 · VCV226727

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 5.52%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Waardenburg syndrome type 2A

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 0.75, phastCons 1
Overall
CADD	13.56	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.52% African / African-American · 4,142/75,034 alleles

Filtering AF 5.38% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.32%

Overall 0.317% 5,121/1,614,174 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.52%	18
Admixed American	0.506%	197
Remaining individualsnot grpmax-eligible	0.469%	213
Middle Eastern	0.445%	225
European (non-Finnish)	0.0291%	3,440
South Asian	0.011%	9,108
East Asian	0.00446%	22,438

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.Thr110=
Coding: c.330G>A
MANE Select: NM_001354604
dbSNP: rs9849776
Type: single nucleotide variant
Location: chr3:69879359 (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: melanoma, cutaneous malignant, susceptibility to, 8

Similar variants

MITF p.Thr110Met Conflicting classifications of pathogenicity ★ ⚠ 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
MITF c.956-1G>A Pathogenic ★★ same condition
MITF p.Arg217Ter Pathogenic/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-thr110 (accessed [today's date]).

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