Is CEL p.Thr479Ile (c.1436C>T) pathogenic?

CEL p.Thr479Ile (c.1436C>T) is classified Uncertain significance in CEL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-10-31). Ultra-rare (popmax 0.0486%, amr).

How common is CEL p.Thr479Ile (c.1436C>T) in the general population?

CEL p.Thr479Ile (c.1436C>T) is ultra-rare (popmax 0.0486%, amr) (gnomAD).

CEL p.Thr479Ile

c.1436C>T · rs201677850 · VCV1191685

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0486%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.144	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -0.48, phastCons 0.97
Regional constraint	o/e 0.75	unconstrained · MANE · 651 bp · p 0.0028 · regional, not allelic
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0486% Admixed American · 28/57,664 alleles

Filtering AF 0.0415% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0402%

Overall 0.0382% 607/1,590,202 alleles · ultra-rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.121%	824
Admixed Americangrpmax	0.0486%	2,059
European (non-Finnish)	0.0446%	2,240
Remaining individualsnot grpmax-eligible	0.0291%	3,432
African / African-American	0.0176%	5,679
Ashkenazi Jewishnot grpmax-eligible	0.0174%	5,746
East Asian	0.0135%	7,406
South Asian	0.0111%	9,019
Finnishnot grpmax-eligible	0.0097%	10,313

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.Thr479Ile
Coding: c.1436C>T
MANE Select: NM_001807
dbSNP: rs201677850
Type: single nucleotide variant
Location: chr9:133070610 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 479: an α-helix

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-thr479ile (accessed [today's date]).

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