Is AGR2 p.Pro71Thr (c.211C>A) pathogenic?

AGR2 p.Pro71Thr (c.211C>A) is classified Likely pathogenic in AGR2 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-03-25). AlphaMissense: likely pathogenic (0.9822); Absent from gnomAD v4.1; Associated with respiratory infections, recurrent, and failure to thrive with or without diarrhea.

How common is AGR2 p.Pro71Thr (c.211C>A) in the general population?

AGR2 p.Pro71Thr (c.211C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGR2 p.Pro71Thr (c.211C>A)?

AlphaMissense predicts likely pathogenic (score 0.9822) — an in-silico prediction, not a clinical call.

AGR2 p.Pro71Thr

Q: What condition is associated with AGR2 p.Pro71Thr (c.211C>A)?

AGR2 p.Pro71Thr (c.211C>A) is associated with respiratory infections, recurrent, and failure to thrive with or without diarrhea (ClinVar).

c.211C>A · rs2534653268 · VCV2443885

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9822 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.9822	likely pathogenic ✓ concordant with ClinVar
REVEL	0.721	pathogenic-leaning
SaProt	LLR -15.85	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 8,885 bp · p 0.18 · regional, not allelic
Overall
CADD	28.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AGR2
Protein: p.Pro71Thr
Coding: c.211C>A
MANE Select: NM_006408
dbSNP: rs2534653268
Type: single nucleotide variant
Location: chr7:16801196 (GRCh38)
Gene constraint: LOEUF 1.34 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.52 · 5 PDB
Residue 71: a UniProt-annotated variant site (in riftd; uncertain significance)

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 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.Tyr111Cys Uncertain significance ★ ⚠ same condition
AGR2 p.Gly143Glu Pathogenic same condition
AGR2 p.Asp35fs Likely pathogenic ★ same condition
AGR2 p.His83fs Pathogenic ★ same condition
AGR2 p.Asp32fs 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/agr2-p-pro71thr (accessed [today's date]).

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