CEL p.Val692fs
c.2073dup · rs756449511 · VCV3383333
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (11 of 11) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -0.28 | GERP -0.18 |
| Overall | ||
| CADD | 22.7 | PHRED · no single calibrated threshold — expert panels disagree |
| Region caveats | ||
| Repeat context | tandem | chr9:133080625 segmental duplication, simple repeat · ambiguous alignment · reads may not map uniquely · confidence, not pathogenicity |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 0.359% | 279 |
| Remaining individualsnot grpmax-eligible | 0.107% | 934 |
| European (non-Finnish)grpmax | 0.101% | 986 |
| Admixed American | 0.0745% | 1,342 |
| Middle Eastern | 0.0481% | 2,078 |
| African / African-American | 0.0141% | 7,111 |
| South Asian | 0.00958% | 10,441 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00757% | 13,210 |
| East Asian | 0.00423% | 23,644 |
Finnish 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.Val692fs
- Coding
- c.2073dup
- MANE Select
- NM_001807
- dbSNP
- rs756449511
- Type
- Duplication
- Location
- chr9:133071567 (GRCh38)
- Gene constraint
- LOEUF 0.972 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.10 · 7 PDB
- Residue 692
- the 'disordered' region; the '17 x 11 aa tandem repeats, glycodomain, o-linked (mucin type)' region
Disease context
maturity-onset diabetes of the young type 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor MODY (Orphanet):
- Inheritance
- Autosomal dominant, Not applicable
- Onset
- Adolescent, Adult, Childhood
- Prevalence
- 1-5 / 10 000 (Europe)
Similar variants
- CEL c.895+2dup Uncertain significance ★★ same condition
- CEL p.Val714fs Likely pathogenic ★ same condition
- CEL p.Asp204fs Uncertain significance ★ same condition
- CEL p.Gly688_Ala689insProProProValProProThrGlyAspSerGly Uncertain significance ★ same condition
- CEL p.Thr695fs Uncertain significance ★ same condition
- CEL p.Val604fs Uncertain significance ★ same condition
- CEL p.Val637fs Uncertain significance ★ same condition
- CEL p.Val681fs 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-val692fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown