Is WDR72 p.Val33= (c.99G>T) pathogenic?

WDR72 p.Val33= (c.99G>T) is classified Conflicting classifications of pathogenicity in WDR72 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-01-21). Rare (popmax 0.413%, nfe); Associated with amelogenesis imperfecta hypomaturation type 2A3.

What condition is associated with WDR72 p.Val33= (c.99G>T)?

WDR72 p.Val33= (c.99G>T) is associated with amelogenesis imperfecta hypomaturation type 2A3 (ClinVar).

How common is WDR72 p.Val33= (c.99G>T) in the general population?

WDR72 p.Val33= (c.99G>T) is rare (popmax 0.413%, nfe) (gnomAD).

WDR72 p.Val33=

c.99G>T · rs144767107 · VCV316604

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.413%, nfe)

Conditions

amelogenesis imperfecta hypomaturation type 2A3

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 0.75	GERP -2.9, phastCons 1
Overall
CADD	3.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.413% European (non-Finnish) · 4,870/1,179,960 alleles

Filtering AF 0.403% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.399%

Overall 0.338% 5,453/1,614,026 alleles · rare exomes 5,118/1,461,798 · genomes 335/152,228 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.413%	242
Middle Eastern	0.297%	337
Remaining individualsnot grpmax-eligible	0.28%	357
South Asian	0.267%	375
Admixed American	0.1%	1,000
African / African-American	0.0693%	1,442
Finnishnot grpmax-eligible	0.0422%	2,371
Ashkenazi Jewishnot grpmax-eligible	0.0236%	4,229
East Asian	0.00223%	44,866

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: WDR72
Protein: p.Val33=
Coding: c.99G>T
MANE Select: NM_182758
dbSNP: rs144767107
Type: single nucleotide variant
Location: chr15:53733051 (GRCh38)
Gene constraint: LOEUF 1.089 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.22

Full WDR72 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

amelogenesis imperfecta hypomaturation type 2A3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

WDR72 p.Arg30Ter Pathogenic/Likely pathogenic ★★ same condition
WDR72 p.Arg896Ter Pathogenic/Likely pathogenic ★★ same condition
WDR72 p.Lys333Ter Pathogenic ★★ same condition
WDR72 p.Trp978Ter Pathogenic ★★ same condition
WDR72 c.*3852T>G Uncertain significance ★★ same condition
WDR72 p.Ala1094Thr Uncertain significance ★★ ⚠ same condition
WDR72 p.Ala373Val Uncertain significance ★★ ⚠ same condition
WDR72 p.Ala402Val Uncertain significance ★★ ⚠ 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/wdr72-p-val33 (accessed [today's date]).

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