Is CELA2A p.Trp191Ter (c.572G>A) pathogenic?

CELA2A p.Trp191Ter (c.572G>A) is classified Likely pathogenic in CELA2A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-22). Very rare (popmax 0.000424%, nfe); Associated with abdominal obesity-metabolic syndrome 4.

What condition is associated with CELA2A p.Trp191Ter (c.572G>A)?

CELA2A p.Trp191Ter (c.572G>A) is associated with abdominal obesity-metabolic syndrome 4 (ClinVar).

How common is CELA2A p.Trp191Ter (c.572G>A) in the general population?

CELA2A p.Trp191Ter (c.572G>A) is very rare (popmax 0.000424%, nfe) (gnomAD).

CELA2A p.Trp191Ter

c.572G>A · VCV3385400

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Conditions

abdominal obesity-metabolic syndrome 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 8
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,030 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,862 alleles · very rare

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: CELA2A
Protein: p.Trp191Ter
Coding: c.572G>A
MANE Select: NM_033440
Type: single nucleotide variant
Location: chr1:15466077 (GRCh38)
Gene constraint: LOEUF 1.161 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.66
Residue 191: the peptidase s1 domain; a disulfide bond

Full CELA2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

abdominal obesity-metabolic syndrome 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CELA2A p.Leu85Met Likely pathogenic ★★ ⚠ same condition
CELA2A p.Thr70Met Pathogenic ★★ same condition
CELA2A c.356+5G>C Uncertain significance ★ same condition
CELA2A p.Ile148Val Uncertain significance ★ ⚠ same condition
CELA2A p.Leu127Met Uncertain significance ★ ⚠ same condition
CELA2A c.639+1G>C Pathogenic same condition
CELA2A p.Asp121Asn Pathogenic same condition
CELA2A p.Gln230Glu Likely benign ★★ 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/cela2a-p-trp191ter (accessed [today's date]).

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