Is CEL p.Pro647Ala (c.1939C>G) pathogenic?

CEL p.Pro647Ala (c.1939C>G) is classified Uncertain significance in CEL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-27). Rare (popmax 0.122%, afr); Associated with Inborn genetic diseases.

What condition is associated with CEL p.Pro647Ala (c.1939C>G)?

CEL p.Pro647Ala (c.1939C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CEL p.Pro647Ala (c.1939C>G) in the general population?

CEL p.Pro647Ala (c.1939C>G) is rare (popmax 0.122%, afr) (gnomAD).

CEL p.Pro647Ala

c.1939C>G · rs1461682199 · VCV2225036

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.122%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.218	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.39	GERP 0.26, phastCons 0.005
Regional constraint	o/e 1.11	unconstrained · MANE · 642 bp · p 0.096 · regional, not allelic
Overall
CADD	13.84	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.122% African / African-American · 14/11,494 alleles

Filtering AF 0.0736% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0589%

Overall 0.013% 18/138,574 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.122%	821
Admixed American	0.037%	2,699
Remaining individualsnot grpmax-eligible	0.0181%	5,538

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.Pro647Ala
Coding: c.1939C>G
MANE Select: NM_001807
dbSNP: rs1461682199
Type: single nucleotide variant
Location: chr9:133071441 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 647: 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.Pro647His Uncertain significance ★ 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
CEL p.Gly147Ser 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-pro647ala (accessed [today's date]).

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