Is MITF p.Ala384Thr (c.1150G>A) pathogenic?

MITF p.Ala384Thr (c.1150G>A) is classified Conflicting classifications of pathogenicity in MITF (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.0907); Rare (popmax 0.115%, mid); Associated with Tietz syndrome.

What condition is associated with MITF p.Ala384Thr (c.1150G>A)?

MITF p.Ala384Thr (c.1150G>A) is associated with Tietz syndrome, Waardenburg syndrome type 2A, melanoma, cutaneous malignant, susceptibility to, 8 (ClinVar).

How common is MITF p.Ala384Thr (c.1150G>A) in the general population?

MITF p.Ala384Thr (c.1150G>A) is rare (popmax 0.115%, mid) (gnomAD).

What do computational predictors say about MITF p.Ala384Thr (c.1150G>A)?

AlphaMissense predicts likely benign (score 0.0907) — an in-silico prediction, not a clinical call.

MITF p.Ala384Thr

c.1150G>A · rs202020443 · VCV666714

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0907 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.115%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Tietz syndrome

Computational evidence

Protein change
AlphaMissense	0.0907	likely benign
REVEL	0.35	indeterminate
SaProt	LLR -8.54	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.1, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 5,907 bp · p 0.32 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.115% Middle Eastern · 7/6,076 alleles

Filtering AF 0.0663% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0608%

Overall 0.0108% 175/1,613,790 alleles · rare exomes 165/1,461,598 · genomes 10/152,192 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.115%	868
South Asian	0.0813%	1,231
Remaining individualsnot grpmax-eligible	0.0176%	5,679
Admixed American	0.00834%	11,998
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,800
European (non-Finnish)	0.00619%	16,163
African / African-American	0.00267%	37,457
Finnishnot grpmax-eligible	0.00156%	64,034

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.Ala384Thr
Coding: c.1150G>A
MANE Select: NM_001354604
dbSNP: rs202020443
Type: single nucleotide variant
Location: chr3:69959391 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.25 · 12 PDB
Residue 384: the 'leucine-zipper' region; an α-helix

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

Disease context

Tietz syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Waardenburg syndrome type 2A melanoma, cutaneous malignant, susceptibility to, 8

Similar variants

MITF p.Ala384Ser Uncertain significance ★★ ⚠ same residue
MITF p.Ala384= 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
MITF c.956-1G>A 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-ala384thr (accessed [today's date]).

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