Is CEL p.Pro724= (c.2172T>C) pathogenic?

CEL p.Pro724= (c.2172T>C) is classified Likely benign in CEL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-01). Rare (popmax 0.327%, afr).

How common is CEL p.Pro724= (c.2172T>C) in the general population?

CEL p.Pro724= (c.2172T>C) is rare (popmax 0.327%, afr) (gnomAD).

CEL p.Pro724=

c.2172T>C · rs200971679 · VCV2659686

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.327%, afr)

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 -20	GERP -0.77
Overall
CADD	0.155	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.327% African / African-American · 170/51,960 alleles

Filtering AF 0.287% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.272%

Overall 0.0529% 785/1,484,354 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.43%	70
African / African-Americangrpmax	0.327%	306
Middle Eastern	0.269%	372
Admixed American	0.104%	961
Finnishnot grpmax-eligible	0.064%	1,562
Remaining individualsnot grpmax-eligible	0.055%	1,817
East Asian	0.053%	1,888
South Asian	0.0426%	2,348
European (non-Finnish)	0.0369%	2,709
Ashkenazi Jewishnot grpmax-eligible	0.0184%	5,425

Amish 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.Pro724=
Coding: c.2172T>C
MANE Select: NM_001807
dbSNP: rs200971679
Type: single nucleotide variant
Location: chr9:133071674 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 724: 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 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
CEL p.Asn37Ser 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-pro724 (accessed [today's date]).

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