Is CEL p.Ala722Thr (c.2164G>A) pathogenic?

CEL p.Ala722Thr (c.2164G>A) is classified Uncertain significance in CEL (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-10). Ultra-rare (popmax 0.0424%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CEL p.Ala722Thr (c.2164G>A)?

CEL p.Ala722Thr (c.2164G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CEL p.Ala722Thr (c.2164G>A) in the general population?

CEL p.Ala722Thr (c.2164G>A) is ultra-rare (popmax 0.0424%, nfe) (gnomAD).

CEL p.Ala722Thr

c.2164G>A · rs202034862 · VCV2391783

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0424%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.109	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.08	GERP 0.43
Regional constraint	o/e 1.11	unconstrained · MANE · 642 bp · p 0.096 · regional, not allelic
Overall
CADD	15.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0424% European (non-Finnish) · 489/1,154,080 alleles

Filtering AF 0.0393% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.038%

Overall 0.034% 536/1,577,512 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0424%	2,360
Finnishnot grpmax-eligible	0.0357%	2,802
Admixed American	0.022%	4,552
Remaining individualsnot grpmax-eligible	0.0098%	10,201
African / African-American	0.00561%	17,825
East Asian	0.00456%	21,924

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.Ala722Thr
Coding: c.2164G>A
MANE Select: NM_001807
dbSNP: rs202034862
Type: single nucleotide variant
Location: chr9:133071666 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 722: 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.Ala722Val Uncertain significance ★★ same residue
CEL p.Ala722= Likely benign ★ same residue
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

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-ala722thr (accessed [today's date]).

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