Is AGR2 p.Asp35fs (c.104del) pathogenic?

AGR2 p.Asp35fs (c.104del) is classified Likely pathogenic in AGR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-04). Associated with respiratory infections, recurrent, and failure to thrive with or without diarrhea.

AGR2 p.Asp35fs

Q: What condition is associated with AGR2 p.Asp35fs (c.104del)?

AGR2 p.Asp35fs (c.104del) is associated with respiratory infections, recurrent, and failure to thrive with or without diarrhea (ClinVar).

c.104del · VCV3384114

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

respiratory infections, recurrent, and failure to thrive with or without diarrhea

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.69	GERP 0.55, phastCons 0.14

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

Variant & gene context

Gene: AGR2
Protein: p.Asp35fs
Coding: c.104del
MANE Select: NM_006408
Type: Deletion
Location: chr7:16801693 (GRCh38)
Gene constraint: LOEUF 1.34 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.52 · 5 PDB
Residue 35: the 'required to promote cell adhesion' region

Full AGR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

respiratory infections, recurrent, and failure to thrive with or without diarrhea — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AGR2 p.Asp32fs Uncertain significance ★ same condition
AGR2 c.256+2T>C Likely pathogenic ★ same condition
AGR2 c.330+1G>T Pathogenic ★ same condition
AGR2 p.His117Tyr Likely pathogenic ★ ⚠ same condition
AGR2 p.His83fs Pathogenic ★ same condition
AGR2 p.Pro71Thr Likely pathogenic ★ same condition
AGR2 p.Tyr111Cys Uncertain significance ★ ⚠ same condition
AGR2 p.Gly143Glu Pathogenic 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/agr2-p-asp35fs (accessed [today's date]).

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