Is CEL p.Pro594Thr (c.1780C>A) pathogenic?

CEL p.Pro594Thr (c.1780C>A) is classified Benign in CEL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-01). Rare (popmax 0.134%, mid).

How common is CEL p.Pro594Thr (c.1780C>A) in the general population?

CEL p.Pro594Thr (c.1780C>A) is rare (popmax 0.134%, mid) (gnomAD).

CEL p.Pro594Thr

c.1780C>A · VCV3771078

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.134%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.116	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.16	GERP -1.5
Regional constraint	o/e 1.11	unconstrained · MANE · 642 bp · p 0.096 · regional, not allelic
Overall
CADD	15.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.134% Middle Eastern · 7/5,228 alleles

Filtering AF 0.102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0945%

Overall 0.0205% 288/1,408,254 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.32%	312
Middle Easterngrpmax	0.134%	747
South Asian	0.121%	824
Remaining individualsnot grpmax-eligible	0.0375%	2,666
Finnishnot grpmax-eligible	0.0189%	5,285
East Asian	0.0153%	6,527
Admixed American	0.0145%	6,908
African / African-American	0.00816%	12,258
European (non-Finnish)	0.00477%	20,963

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.Pro594Thr
Coding: c.1780C>A
MANE Select: NM_001807
Type: single nucleotide variant
Location: chr9:133071282 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 594: 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.Pro594= Likely benign ★★ same residue
CEL c.67-3C>A Uncertain significance ★★ same type
CEL p.Ala295Ser Uncertain significance ★★ same type
CEL p.Ala548Glu Uncertain significance ★★ same type
CEL p.Ala722Val Uncertain significance ★★ same type
CEL p.Arg116Gln Uncertain significance ★★ same type
CEL p.Arg185Trp Uncertain significance ★★ same type
CEL p.Arg443Trp Uncertain significance ★★ same type

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-pro594thr (accessed [today's date]).

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