Is CEL p.Pro678fs (c.2030_2031insC) pathogenic?

CEL p.Pro678fs (c.20302031insC) is classified Likely benign in CEL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-16). Very rare (popmax 0.000487%, nfe).

How common is CEL p.Pro678fs (c.2030_2031insC) in the general population?

CEL p.Pro678fs (c.2030_2031insC) is very rare (popmax 0.000487%, nfe) (gnomAD).

CEL p.Pro678fs

c.2030_2031insC · rs1166247791 · VCV3910775

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000487%, nfe)

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 -6.3	GERP -0.066
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

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000487% European (non-Finnish) · 3/616,634 alleles

Filtering AF 0.00013% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.6e-05%

Overall 0.000534% 4/748,620 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00324%	30,830
European (non-Finnish)grpmax	0.000487%	205,545

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.Pro678fs
Coding: c.2030_2031insC
MANE Select: NM_001807
dbSNP: rs1166247791
Type: Insertion
Location: chr9:133071532 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 678: 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

Similar variants

CEL p.Pro678Ala Likely benign ★★ same residue

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-pro678fs (accessed [today's date]).

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