Is CEL p.Ala612Gly (c.1835C>G) pathogenic?

CEL p.Ala612Gly (c.1835C>G) is classified Conflicting classifications of pathogenicity in CEL (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-01). Rare (popmax 0.15%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CEL p.Ala612Gly (c.1835C>G)?

CEL p.Ala612Gly (c.1835C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CEL p.Ala612Gly (c.1835C>G) in the general population?

CEL p.Ala612Gly (c.1835C>G) is rare (popmax 0.15%, nfe) (gnomAD).

CEL p.Ala612Gly

c.1835C>G · rs1329061274 · VCV2343258

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.15%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.095	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.2	GERP -0.68
Regional constraint	o/e 1.11	unconstrained · MANE · 642 bp · p 0.096 · regional, not allelic
Overall
CADD	8.476	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.15% European (non-Finnish) · 289/192,864 alleles

Filtering AF 0.136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.13%

Overall 0.102% 339/331,946 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.15%	667
Remaining individualsnot grpmax-eligible	0.142%	706
Middle Eastern	0.0821%	1,218
Finnishnot grpmax-eligible	0.069%	1,448
African / African-American	0.0226%	4,425
Admixed American	0.0133%	7,535
South Asian	0.00951%	10,514

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.Ala612Gly
Coding: c.1835C>G
MANE Select: NM_001807
dbSNP: rs1329061274
Type: single nucleotide variant
Location: chr9:133071337 (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.Ala612Pro 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-ala612gly (accessed [today's date]).

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