Is CEL c.669+6G>A pathogenic?

CEL c.669+6G>A is classified Uncertain significance in CEL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-28). Very rare (popmax 0.00333%, amr); Associated with maturity-onset diabetes of the young type 8.

What condition is associated with CEL c.669+6G>A?

CEL c.669+6G>A is associated with maturity-onset diabetes of the young type 8 (ClinVar).

How common is CEL c.669+6G>A in the general population?

CEL c.669+6G>A is very rare (popmax 0.00333%, amr) (gnomAD).

How is MODY inherited?

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

CEL c.669+6G>A

VCV3596542

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

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
Splice region	donor +6	donor splice region (+6, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.22	GERP -2.7
Non-coding constraint	Z 4.27	1 kb window · o/e 0.75 · regional · uncalibrated
Overall
CADD	11.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,978 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00112% 18/1,612,706 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,989
African / African-American	0.00267%	37,445
European (non-Finnish)	0.00119%	84,242

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
Coding: c.669+6G>A
MANE Select: NM_001807
Type: single nucleotide variant
Location: chr9:133066666 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB

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-c-669-plus-6g-a (accessed [today's date]).

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