Is CEL p.Pro572= (c.1716C>G) pathogenic?

CEL p.Pro572= (c.1716C>G) is classified Likely benign in CEL (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-01). Ultra-rare (popmax 0.0481%, nfe); Associated with maturity-onset diabetes of the young type 8.

What condition is associated with CEL p.Pro572= (c.1716C>G)?

CEL p.Pro572= (c.1716C>G) is associated with maturity-onset diabetes of the young type 8 (ClinVar).

How common is CEL p.Pro572= (c.1716C>G) in the general population?

CEL p.Pro572= (c.1716C>G) is ultra-rare (popmax 0.0481%, nfe) (gnomAD).

How is MODY inherited?

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

CEL p.Pro572=

c.1716C>G · rs200152972 · VCV1202123

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0481%, nfe)

Conditions

maturity-onset diabetes of the young type 8

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 -6.1	GERP -2.4
Overall
CADD	0.078	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0481% European (non-Finnish) · 565/1,174,040 alleles

Filtering AF 0.0448% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0435%

Overall 0.051% 813/1,594,196 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.349%	287
Finnishnot grpmax-eligible	0.0776%	1,289
European (non-Finnish)grpmax	0.0481%	2,078
Remaining individualsnot grpmax-eligible	0.0403%	2,480
African / African-American	0.038%	2,633
Middle Eastern	0.0331%	3,020
South Asian	0.031%	3,230
Admixed American	0.027%	3,710
East Asian	0.0113%	8,859

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CEL
Protein: p.Pro572=
Coding: c.1716C>G
MANE Select: NM_001807
dbSNP: rs200152972
Type: single nucleotide variant
Location: chr9:133071218 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 572: the 'disordered' region; the '17 x 11 aa tandem repeats, glycodomain, o-linked (mucin type)' region

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

Disease context

maturity-onset diabetes of the young type 8 — 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

CEL c.67-3C>A Uncertain significance ★★ same condition
CEL p.Ala295Ser Uncertain significance ★★ same condition
CEL p.Ala548Glu Uncertain significance ★★ same condition
CEL p.Ala722Val Uncertain significance ★★ same condition
CEL p.Arg116Gln Uncertain significance ★★ same condition
CEL p.Arg185Trp Uncertain significance ★★ same condition
CEL p.Arg443Trp Uncertain significance ★★ same condition
CEL p.Asn37Ser 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/cel-p-pro572 (accessed [today's date]).

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