Is DLX3 p.Pro30= (c.90T>C) pathogenic?

DLX3 p.Pro30= (c.90T>C) is classified Conflicting classifications of pathogenicity in DLX3 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-01). Low-frequency (popmax 1.12%, mid); Associated with hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism.

What condition is associated with DLX3 p.Pro30= (c.90T>C)?

DLX3 p.Pro30= (c.90T>C) is associated with hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism (ClinVar).

How common is DLX3 p.Pro30= (c.90T>C) in the general population?

DLX3 p.Pro30= (c.90T>C) is low-frequency (popmax 1.12%, mid) (gnomAD).

How is Amelogenesis imperfecta inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DLX3 p.Pro30=

c.90T>C · rs145424773 · VCV193301

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.12%, mid)

Conditions

hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism

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 3.9	GERP -1.2, phastCons 1
Overall
CADD	14.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.12% Middle Eastern · 68/6,052 alleles

Filtering AF 0.909% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.831%

Overall 0.0251% 405/1,614,154 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.12%	89
Ashkenazi Jewishnot grpmax-eligible	0.101%	987
Admixed American	0.0616%	1,622
Remaining individualsnot grpmax-eligible	0.0576%	1,736
African / African-American	0.0213%	4,692
European (non-Finnish)	0.0173%	5,784
South Asian	0.011%	9,109
Finnishnot grpmax-eligible	0.00625%	15,994

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: DLX3
Protein: p.Pro30=
Coding: c.90T>C
MANE Select: NM_005220
dbSNP: rs145424773
Type: single nucleotide variant
Location: chr17:49994909 (GRCh38)
Gene constraint: LOEUF 0.559 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 60.87 · 1 PDB
Residue 30: the 'disordered' region

Full DLX3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Amelogenesis imperfecta (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked dominant
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (United States)

Similar variants

DLX3 p.Pro30Thr Uncertain significance ★ ⚠ same residue
DLX3 p.Asn282Lys Uncertain significance ★★ ⚠ same condition
DLX3 p.Gln47Arg Uncertain significance ★★ ⚠ same condition
DLX3 p.Pro233Leu Uncertain significance ★★ ⚠ same condition
DLX3 c.516+23C>T Benign ★★ same condition
DLX3 c.-134C>A Benign ★★ same condition
DLX3 c.-189G>T Benign ★★ same condition
DLX3 c.-64C>T Benign ★★ 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/dlx3-p-pro30 (accessed [today's date]).

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