Is CEL p.Ala612Pro (c.1834G>C) pathogenic?

CEL p.Ala612Pro (c.1834G>C) is classified Conflicting classifications of pathogenicity in CEL (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2024-11-20). Rare (popmax 0.285%, afr); Associated with Inborn genetic diseases.

What condition is associated with CEL p.Ala612Pro (c.1834G>C)?

CEL p.Ala612Pro (c.1834G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CEL p.Ala612Pro (c.1834G>C) in the general population?

CEL p.Ala612Pro (c.1834G>C) is rare (popmax 0.285%, afr) (gnomAD).

CEL p.Ala612Pro

c.1834G>C · rs1322454680 · VCV1175054

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.285%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.132	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.022	GERP -1.2
Regional constraint	o/e 1.11	unconstrained · MANE · 642 bp · p 0.096 · regional, not allelic
Overall
CADD	17.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.285% African / African-American · 27/9,460 alleles

Filtering AF 0.247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.24%

Overall 0.209% 729/349,150 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.285%	350
European (non-Finnish)	0.265%	377
Remaining individualsnot grpmax-eligible	0.22%	454
South Asian	0.201%	498
Middle Eastern	0.153%	653
Admixed American	0.0899%	1,112
Finnishnot grpmax-eligible	0.0484%	2,068
East Asian	0.0295%	3,389

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.Ala612Pro
Coding: c.1834G>C
MANE Select: NM_001807
dbSNP: rs1322454680
Type: single nucleotide variant
Location: chr9:133071336 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 612: 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.Ala612Gly Conflicting classifications of pathogenicity ★ same residue
CEL p.Ala612Thr 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-ala612pro (accessed [today's date]).

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