Is PDX1 p.Pro244= (c.732C>G) pathogenic?

PDX1 p.Pro244= (c.732C>G) is classified Benign/Likely benign in PDX1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-06-22). Ultra-rare (popmax 0.0433%, nfe); Associated with maturity-onset diabetes of the young.

What condition is associated with PDX1 p.Pro244= (c.732C>G)?

PDX1 p.Pro244= (c.732C>G) is associated with maturity-onset diabetes of the young (ClinVar).

How common is PDX1 p.Pro244= (c.732C>G) in the general population?

PDX1 p.Pro244= (c.732C>G) is ultra-rare (popmax 0.0433%, nfe) (gnomAD).

How is MODY inherited?

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

PDX1 p.Pro244=

c.732C>G · rs777512281 · VCV390803

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0433%, nfe)

Conditions

maturity-onset diabetes of the young

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 -9.1	GERP -5.1
Overall
CADD	1.303	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0433% European (non-Finnish) · 490/1,131,190 alleles

Filtering AF 0.0401% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0388%

Overall 0.034% 511/1,503,956 alleles · ultra-rare exomes 471/1,351,702 · genomes 40/152,254 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0433%	2,309
Admixed American	0.0192%	5,216
Remaining individualsnot grpmax-eligible	0.0137%	7,288
Finnishnot grpmax-eligible	0.00588%	17,019
African / African-American	0.00143%	70,152

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: PDX1
Protein: p.Pro244=
Coding: c.732C>G
MANE Select: NM_000209
dbSNP: rs777512281
Type: single nucleotide variant
Location: chr13:27924581 (GRCh38)
Gene constraint: LOEUF 1.642 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.99 · 2 PDB
Residue 244: the 'disordered' region

Full PDX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For MODY (Orphanet):

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

Similar variants

PDX1 p.Pro244_Gly245insPro Conflicting classifications of pathogenicity ★ same residue
PDX1 p.Pro244Arg Uncertain significance ★ ⚠ same residue
PDX1 p.Ala10Thr Uncertain significance ★★ ⚠ same condition
PDX1 p.Asp226Ala Uncertain significance ★★ ⚠ same condition
PDX1 p.Ile190Thr Uncertain significance ★★ ⚠ same condition
PDX1 p.Pro244_Gly245insArg Uncertain significance ★★ same residue
PDX1 p.Ala275= Likely benign ★★ same condition
PDX1 p.Arg176= Likely 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/pdx1-p-pro244 (accessed [today's date]).

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