# NM_024740.2(ALG9):c.1602+14del

https://sugi.bio/variant/alg9-c-1602-plus-14del

## Summary

**ALG9 c.1602+14del** is classified **Likely benign** in ALG9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-19). Associated with ALG9-congenital disorder of glycosylation.

**At a glance:** Likely benign · review: Single submitter · 1 submitter · 1 linked condition

## For patients & families {#patients}

This is a change in the ALG9 gene that is classified as likely benign — not considered disease-causing, submitted by 1 submitter, and is linked to ALG9-congenital disorder of glycosylation.

*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 recessive |
| Age of onset (of this condition) | Antenatal, Infancy, Neonatal |
| Diagnostic panels | ALG9 is a diagnostic-grade gene on 16 Genomics England panels |

**Commonly reported features of ALG9-CDG** (across patients with this condition; presentation varies — frequencies from Orphanet):

- Intellectual disability — Very frequent (99-80%)
- Seizure — Very frequent (99-80%)
- Global developmental delay — Very frequent (99-80%)
- Progressive microcephaly — Frequent (79-30%)
- Hypotonia — Frequent (79-30%)
- Abnormal heart morphology — Frequent (79-30%)
- Pericardial effusion — Frequent (79-30%)
- Hepatomegaly — Frequent (79-30%)

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0009839/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [ALG9](https://sugi.bio/atlas/gene/ALG9/) |
| Coding change (HGVS c.) | c.1602+14del |
| MANE Select transcript | [NM_024740](https://www.ncbi.nlm.nih.gov/nuccore/NM_024740) |
| Variant type | Deletion |
| Location | chr11:111836151-111836151 (GRCh38) |
| ClinVar | [VCV3730397](https://www.ncbi.nlm.nih.gov/clinvar/variation/3730397/) |

**All HGVS expressions:** `NC_000011.10:g.111836152del`, `NC_000011.9:g.111706875del`, `NG_009210.1:g.40431del`, `NG_009210.2:g.40430del`, `NM_001077690.1:c.1581+14del`, `NM_001077691.2:c.1089+14del`, `NM_001077692.2:c.1068+14del`, `NM_001352409.1:c.1068+14del`, `NM_001352410.1:c.1068+14del`, `NM_001352411.2:c.1068+14del`, `NM_001352412.2:c.1068+14del`, `NM_001352413.1:c.1089+14del`, `NM_001352414.2:c.1089+14del`, `NM_001352415.1:c.1068+14del`, `NM_001352416.1:c.1068+14del`, `NM_001352417.1:c.1581+14del`, `NM_001352418.1:c.1458+14del`, `NM_001352419.1:c.1089+14del`, `NM_001352420.2:c.1068+14del`, `NM_001352421.2:c.1068+14del`, `NM_001352422.2:c.993+14del`, `NM_001352423.2:c.945+14del`, `NM_024740.2:c.1602+14del`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP 1.9, GERP -0.801, phastCons 1 — weakly conserved position
- Splice region: **near-intronic (+14 nt from the splice site)**.
- Non-coding constraint (Gnocchi): **Z 1.72**, o/e 0.87 (1 kb window 111,836,000–111,837,000). A higher Z means the window carries less variation than expected. Describes the 1 kb window, not this allele. No ClinGen expert panel references Gnocchi and no ACMG-calibrated threshold exists for it. *Descriptive; no cut-point applied.*
- SpliceAI: **not assessed** — the release is built from a substitutions-only source, so it holds no deletion variants. That is a property of the dataset, not of the variant, and is not evidence against a splicing effect.

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

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

**ALG9** population constraint: LOEUF 0.853, pLI 1.3976e-12, missense-Z 1.7414. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

Curated gene–disease validity (ClinGen):

- **ALG9-associated autosomal dominant polycystic kidney disease** — Definitive (AD)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 88.35, 77% of residues very-high.

**2 experimental structure(s)** (PDB): [9S6S](https://www.rcsb.org/structure/9S6S), [9S6U](https://www.rcsb.org/structure/9S6U).

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

*Describes the biological roles of ALG9 (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:** ALG9's established molecular role includes dol-P-Man:Man(8)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity. In Reactome, ALG9 is annotated in disease pathway(s) including **Defective ALG9 causes CDG-1l**.

**Disease mechanism (Reactome):** ALG9 loss or alteration is curated in [Defective ALG9 causes CDG-1l](https://reactome.org/content/detail/R-HSA-4720454).

### Pathways affected {#pathways}

ALG9 participates in **2 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| ⚕ [Defective ALG9 causes CDG-1l](https://reactome.org/content/detail/R-HSA-4720454) | curated |
| [Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein](https://reactome.org/content/detail/R-HSA-446193) | curated |

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

**Molecular function:** dol-P-Man:Man(8)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity, dol-P-Man:Man(6)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase activity.

**Biological process:** protein N-linked glycosylation, dolichol-linked oligosaccharide biosynthetic process.

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2024-07-19.

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

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Likely benign | criteria provided, single submitter | clinical testing | 2024-07-19 |

## Associated conditions {#conditions}

[ALG9-congenital disorder of glycosylation](https://sugi.bio/atlas/disease/alg9-congenital-disorder-of-glycosylation/).

**Reported phenotype names (ClinVar):** ALG9 congenital disorder of glycosylation, ALG9-CDG, CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Il, CDG Il.

## Similar variants {#similar}

Related ALG9 variant pages (same residue, condition, or type): [ALG9 c.1605_1608del](/variant/alg9-c-1605-1608del), [ALG9 p.Leu235fs](/variant/alg9-p-leu235fs), [ALG9 p.Met331fs](/variant/alg9-p-met331fs), [ALG9 p.Thr43fs](/variant/alg9-p-thr43fs), [ALG9 c.132-13del](/variant/alg9-c-132-minus-13del), [ALG9 c.1734-17del](/variant/alg9-c-1734-minus-17del), [ALG9 c.702-9_702-8del](/variant/alg9-c-702-minus-9-702-minus-8del), [ALG9 c.566-1G>A](/variant/alg9-c-566-minus-1g-a).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); 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 2026-07-14); 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 3730397). 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.*