Is PDX1 p.Pro96= (c.288C>G) pathogenic?

PDX1 p.Pro96= (c.288C>G) is classified Likely benign in PDX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-31). Very rare (popmax 8.63e-05%, nfe); Associated with maturity-onset diabetes of the young.

What condition is associated with PDX1 p.Pro96= (c.288C>G)?

PDX1 p.Pro96= (c.288C>G) is associated with maturity-onset diabetes of the young (ClinVar).

How common is PDX1 p.Pro96= (c.288C>G) in the general population?

PDX1 p.Pro96= (c.288C>G) is very rare (popmax 8.63e-05%, nfe) (gnomAD).

How is MODY inherited?

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

PDX1 p.Pro96=

c.288C>G · rs1046482148 · VCV1797268

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.63e-05%, 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 -1.8	GERP -2.7
Overall
CADD	6.93	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.63e-05% European (non-Finnish) · 1/1,158,820 alleles

Overall 6.36e-05% 1/1,571,866 alleles · very rare exomes 1/1,419,538 · genomes 0/152,328 · joint denominator

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.Pro96=
Coding: c.288C>G
MANE Select: NM_000209
dbSNP: rs1046482148
Type: single nucleotide variant
Location: chr13:27920426 (GRCh38)
Gene constraint: LOEUF 1.642 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.99 · 2 PDB

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.Pro96Ala 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.Ala275= Likely benign ★★ same condition
PDX1 p.Arg176= Likely benign ★★ same condition
PDX1 p.Asn113= Likely benign ★★ same condition
PDX1 p.Asn2= Benign/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-pro96 (accessed [today's date]).

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