Is PAX4 p.Pro23= (c.69T>C) pathogenic?

PAX4 p.Pro23= (c.69T>C) is classified Benign/Likely benign in PAX4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-15). Rare (popmax 0.241%, afr); Associated with maturity-onset diabetes of the young type 9.

What condition is associated with PAX4 p.Pro23= (c.69T>C)?

PAX4 p.Pro23= (c.69T>C) is associated with maturity-onset diabetes of the young type 9, type 2 diabetes mellitus, diabetes mellitus, ketosis-prone (ClinVar).

How common is PAX4 p.Pro23= (c.69T>C) in the general population?

PAX4 p.Pro23= (c.69T>C) is rare (popmax 0.241%, afr) (gnomAD).

How is MODY inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

PAX4 p.Pro23=

c.69T>C · rs116124047 · VCV1320922

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.241%, afr)

Conditions

maturity-onset diabetes of the young type 9

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	GERP -2.8, phastCons 1
Overall
CADD	11.16	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.241% African / African-American · 181/75,038 alleles

Filtering AF 0.212% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.201%

Overall 0.0174% 281/1,614,174 alleles · rare exomes 159/1,461,888 · genomes 122/152,286 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.241%	415
Middle Eastern	0.066%	1,515
Admixed American	0.0183%	5,457
Remaining individualsnot grpmax-eligible	0.0176%	5,683
European (non-Finnish)	0.00627%	15,946

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: PAX4
Protein: p.Pro23=
Coding: c.69T>C
MANE Select: NM_001366110
dbSNP: rs116124047
Type: single nucleotide variant
Location: chr7:127615476 (GRCh38)
Gene constraint: LOEUF 1.056 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.35
Residue 23: a DNA-binding region; the 'pai subdomain' region

Full PAX4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

maturity-onset diabetes of the young type 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: type 2 diabetes mellitus diabetes mellitus, ketosis-prone

For MODY (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

PAX4 p.Pro23Leu Uncertain significance ★★ same residue
PAX4 c.772-1G>A Uncertain significance ★★ same condition
PAX4 p.Arg163Gln Uncertain significance ★★ same condition
PAX4 p.Arg172Gln Uncertain significance ★★ same condition
PAX4 p.Arg172Trp Uncertain significance ★★ same condition
PAX4 p.Arg191His Uncertain significance ★★ same condition
PAX4 p.Arg226Cys Uncertain significance ★★ same condition
PAX4 p.Arg226His 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/pax4-p-pro23 (accessed [today's date]).

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