# NM_003977.2(AIP):c.(?_1)_(*_?)del

https://sugi.bio/variant/aip-c-1

## Summary

**AIP c.(?_1** is classified **Likely pathogenic** in AIP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2012-06-21). Associated with growth hormone secreting pituitary adenoma 1.

**At a glance:** Likely pathogenic · review: No assertion criteria · 1 submitter · 1 linked condition

## For patients & families {#patients}

This is a change in the AIP gene that is considered likely disease-causing, submitted by 1 submitter, and is linked to growth hormone secreting pituitary adenoma 1.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

|  |  |
| --- | --- |
| Typical inheritance (of this condition) | Autosomal dominant |
| Age of onset (of this condition) | Adolescent, Adult, Childhood, Elderly, Infancy |
| Diagnostic panels | AIP is a diagnostic-grade gene on 3 Genomics England panels |

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0024520/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [AIP](https://sugi.bio/atlas/gene/AIP/) |
| Coding change (HGVS c.) | c.(?_1 |
| MANE Select transcript | [NM_003977](https://www.ncbi.nlm.nih.gov/nuccore/NM_003977) |
| Variant type | Deletion |
| ClinVar | [VCV41160](https://www.ncbi.nlm.nih.gov/clinvar/variation/41160/) |

**All HGVS expressions:** `LRG_460t1:c.(?_1)_(*_?)del`, `NM_003977.2:c.(?_1)_(*_?)del`, `NM_003977.2:c.1-?_993+?del`

## Gene constraint & dosage {#gene-context}

**AIP** population constraint: LOEUF 0.626, pLI 0.28135, missense-Z 1.2835. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 91.09, 78% of residues very-high.

**5 experimental structure(s)** (PDB): [2LKN](https://www.rcsb.org/structure/2LKN), [4AIF](https://www.rcsb.org/structure/4AIF), [4APO](https://www.rcsb.org/structure/4APO), [7ZUB](https://www.rcsb.org/structure/7ZUB), [8QMO](https://www.rcsb.org/structure/8QMO).

## What this gene does {#gene-function}

*Describes the biological roles of AIP (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** AIP's established molecular role includes peptidyl-prolyl cis-trans isomerase activity.


### Pathways affected {#pathways}

AIP participates in **2 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Aryl hydrocarbon receptor signalling](https://reactome.org/content/detail/R-HSA-8937144) | curated |
| [Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation](https://reactome.org/content/detail/R-HSA-8950505) | curated |

### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** peptidyl-prolyl cis-trans isomerase activity, GAF domain binding, obsolete unfolded protein binding.

**Biological process:** obsolete protein targeting to mitochondrion, protein maturation.

## Clinical significance {#significance}

**Likely pathogenic** — review status No assertion criteria *(no assertion criteria provided)*, last evaluated 2012-06-21.

**Submitter consensus:** unanimous (1/1 Likely pathogenic).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| GeneReviews | Likely pathogenic | no assertion criteria provided | curation | 2012-06-21 |

## Associated conditions {#conditions}

[growth hormone secreting pituitary adenoma 1](https://sugi.bio/atlas/disease/growth-hormone-secreting-pituitary-adenoma-1/).

**Reported phenotype names (ClinVar):** Somatotroph adenoma, Pituitary tumor, growth hormone-secreting, somatic, SOMATOTROPHINOMA, FAMILIAL, Pituitary adenoma, growth hormone-secreting, ISOLATED FAMILIAL SOMATOTROPINOMA, PITUITARY ADENOMA 1, MULTIPLE TYPES, AIP Familial Isolated Pituitary Adenomas, ACROMEGALY DUE TO PITUITARY ADENOMA 1.

## Similar variants {#similar}

Related AIP variant pages (same residue, condition, or type): [AIP p.Pro167_Trp168insTer](/variant/aip-p-pro167-trp168inster), [AIP p.Gly47_Arg54del](/variant/aip-p-gly47-arg54del), [AIP p.Val101_Leu141del](/variant/aip-p-val101-leu141del), [AIP c.100-1025_279+357del](/variant/aip-c-100-minus-1025-279-plus-357del), [AIP p.Gly23_Glu24del](/variant/aip-p-gly23-glu24del), [AIP p.Ile182fs](/variant/aip-p-ile182fs), [AIP p.Arg271Trp](/variant/aip-p-arg271trp), [AIP p.Arg304Ter](/variant/aip-p-arg304ter).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-06); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-10-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 41160). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*