Is CEL p.Pro726= (c.2178C>G) pathogenic?

CEL p.Pro726= (c.2178C>G) is classified Likely benign in CEL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-05-01). Rare (popmax 0.134%, mid); Associated with Inborn genetic diseases.

What condition is associated with CEL p.Pro726= (c.2178C>G)?

CEL p.Pro726= (c.2178C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CEL p.Pro726= (c.2178C>G) in the general population?

CEL p.Pro726= (c.2178C>G) is rare (popmax 0.134%, mid) (gnomAD).

CEL p.Pro726=

c.2178C>G · rs201677122 · VCV2659687

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.134%, mid)

Conditions

Inborn genetic diseases

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 -4.2	GERP -0.85
Overall
CADD	0.681	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.134% Middle Eastern · 8/5,948 alleles

Filtering AF 0.0669% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0488%

Overall 0.0146% 232/1,590,794 alleles · rare exomes 213/1,446,780 · genomes 19/144,014 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.134%	743
European (non-Finnish)	0.017%	5,887
Remaining individualsnot grpmax-eligible	0.0114%	8,808
Admixed American	0.0102%	9,830
Finnishnot grpmax-eligible	0.00979%	10,218
African / African-American	0.00415%	24,087
South Asian	0.00332%	30,123
East Asian	0.00226%	44,300

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.Pro726=
Coding: c.2178C>G
MANE Select: NM_001807
dbSNP: rs201677122
Type: single nucleotide variant
Location: chr9:133071680 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 726: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEL p.Ala295Ser Uncertain significance ★★ same condition
CEL p.Ala548Glu Uncertain significance ★★ same condition
CEL p.Arg185Trp Uncertain significance ★★ same condition
CEL p.Arg443Trp Uncertain significance ★★ same condition
CEL p.Gln460Arg Uncertain significance ★★ same condition
CEL p.Glu710Lys Uncertain significance ★★ same condition
CEL p.Gly147Ser Uncertain significance ★★ same condition
CEL p.His68Leu 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-pro726 (accessed [today's date]).

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