# NM_001099922.3(ALG13):c.2617G>C (p.Ala873Pro)

https://sugi.bio/variant/alg13-p-ala873pro

## Summary

**ALG13 p.Ala873Pro (c.2617G>C)** is classified **Benign/Likely benign** in ALG13 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.1099); Rare (popmax 0.217%, nfe); Associated with Inborn genetic diseases.

**At a glance:** Benign/Likely benign · review: Multiple submitters · rsID rs142841538 · 9 submitters · 2 linked conditions · AlphaMissense likely benign · rare (popmax 0.217%, nfe)

## For patients & families {#patients}

This is a change in the ALG13 gene that is classified as benign/likely benign — not considered disease-causing, submitted by 9 submitters, and is linked to Inborn genetic diseases.

*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.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [ALG13](https://sugi.bio/atlas/gene/ALG13/) |
| Protein change (HGVS p.) | p.Ala873Pro |
| Coding change (HGVS c.) | c.2617G>C |
| MANE Select transcript | [NM_001099922](https://www.ncbi.nlm.nih.gov/nuccore/NM_001099922) |
| dbSNP | [rs142841538](https://www.ncbi.nlm.nih.gov/snp/rs142841538/) |
| Variant type | single nucleotide variant |
| Location | chrX:111736801-111736801 (GRCh38) |
| ClinVar | [VCV412610](https://www.ncbi.nlm.nih.gov/clinvar/variation/412610/) |

**All HGVS expressions:** `NC_000023.10:g.110980029G>C`, `NC_000023.11:g.111736801G>C`, `NG_016238.1:g.60684G>C`, `NM_001099922.3:c.2617G>C`, `NM_001257230.2:c.2305G>C`, `NM_001257231.2:c.2383G>C`, `NM_001257234.2:c.2305G>C`, `NM_001257237.2:c.2305G>C`, `NM_001324292.2:c.2617G>C`, `NM_001324293.1:c.2131G>C`, `NR_148693.2:n.2345G>C`

## Computational & population evidence {#evidence}

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

- AlphaMissense **likely benign** (0.1099)
- REVEL 0.056 (moderately benign-leaning) — agrees with AlphaMissense
- SaProt LLR -6.085 (tolerated) — agrees with AlphaMissense
- → **In-silico consensus:** AlphaMissense, REVEL and SaProt all call this tolerated
- Conservation: phyloP -0.087, GERP -2.42, phastCons 0.159 — not a conserved position (phyloP < 0.1, ACGS BP7 cut)
- CADD: **PHRED 5.603**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- Regional missense constraint: **o/e 0.94** across the covering region of the MANE Select transcript (111,721,703–111,744,859), spanning 23,156 bp. Chi-square p 0.27. Describes the region, not this allele; gnomAD v4.1.1's own constrained determination. *Descriptive; no ACMG code applied.*
- SpliceAI: **not assessed** — no allele at this position is in our SpliceAI release, either because it lies outside the scored MANE transcript scope or because every allele is below Δ0.2. We cannot tell which, so this claims neither; absence is not evidence against a splicing effect.
- Population frequency (gnomAD v4.1): grpmax **0.217%** (nfe) · FAF95 0.209% · FAF99 0.206% · 1,944/894,233 in the highest group · 2,553/1,208,505 alleles overall — rare (popmax 0.217%, nfe).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| Finnish (not grpmax-eligible) | 0.948% | 105 |
| Remaining individuals (not grpmax-eligible) | 0.221% | 453 |
| European (non-Finnish) (grpmax) | 0.217% | 460 |
| Admixed American | 0.0788% | 1,268 |
| African / African-American | 0.0245% | 4,078 |
| South Asian | 0.0212% | 4,726 |
| Ashkenazi Jewish (not grpmax-eligible) | 0.00454% | 22,006 |

Finnish shows a higher raw frequency than the grpmax group. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and "Remaining individuals" — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

*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}

**ALG13** population constraint: ClinGen dosage — haploinsufficiency 1/3, triplosensitivity 0/3. *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):

- **genetic developmental and epileptic encephalopathy** — Definitive (XL)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 54.42, 18% of residues very-high.

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

*Describes the biological roles of ALG13 (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:** ALG13's established molecular role includes N-acetylglucosaminyldiphosphodolichol N-acetylglucosaminyltransferase activity. In Reactome, ALG13 is annotated in disease pathway(s) including **Defective ALG14 causes ALG14-CMS**.

**Disease mechanism (Reactome):** ALG13 loss or alteration is curated in [Defective ALG14 causes ALG14-CMS](https://reactome.org/content/detail/R-HSA-5633231).

### Pathways affected {#pathways}

ALG13 participates in **2 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| ⚕ [Defective ALG14 causes ALG14-CMS](https://reactome.org/content/detail/R-HSA-5633231) | other |
| [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) | other |

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

**Molecular function:** N-acetylglucosaminyldiphosphodolichol N-acetylglucosaminyltransferase activity.

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

## Clinical significance {#significance}

**Benign/Likely benign** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2026-01-26.

**Submitter consensus:** conflicting (5 Likely benign, 4 Benign).

**Submission history:** 9 submissions (2017–2026); classifications have differed over time.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Athena Diagnostics | Likely benign | criteria provided, single submitter | clinical testing | 2019-04-08 |
| Genome-Nilou Lab | Benign | criteria provided, single submitter | clinical testing | 2021-12-05 |
| Ambry Genetics | Benign | criteria provided, single submitter | clinical testing | 2017-05-31 |
| PreventionGenetics, part of Exact Sciences | Likely benign | no assertion criteria provided | clinical testing | 2019-03-01 |
| Labcorp Genetics (formerly Invitae), Labcorp | Benign | criteria provided, single submitter | clinical testing | 2026-01-26 |
| GeneDx | Benign | criteria provided, single submitter | clinical testing | 2017-02-09 |
| Genome Diagnostics Laboratory, University Medical Center Utrecht | Likely benign | no assertion criteria provided | clinical testing |  |
| Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Likely benign | no assertion criteria provided | clinical testing |  |
| Blueprint Genetics | Likely benign | criteria provided, single submitter | clinical testing | 2024-11-25 |

## Associated conditions {#conditions}

[Inborn genetic diseases](https://sugi.bio/atlas/disease/inborn-genetic-diseases/), [developmental and epileptic encephalopathy, 36](https://sugi.bio/atlas/disease/developmental-and-epileptic-encephalopathy-36/).

**Reported phenotype names (ClinVar):** Inborn genetic diseases, not provided, not specified, Developmental and epileptic encephalopathy, 36, ALG13-related disorder, ALG13-related condition, AllHighlyPenetrant, none provided, Epileptic encephalopathy, early infantile, 36, Congenital disorder of glycosylation, type Is.

## Similar variants {#similar}

Related ALG13 variant pages (same residue, condition, or type): [ALG13 p.Asn107Ser](/variant/alg13-p-asn107ser), [ALG13 c.2458-1G>A](/variant/alg13-c-2458-minus-1g-a), [ALG13 c.2695+4G>A](/variant/alg13-c-2695-plus-4g-a), [ALG13 c.2932+6T>C](/variant/alg13-c-2932-plus-6t-c), [ALG13 c.834+3A>G](/variant/alg13-c-834-plus-3a-g), [ALG13 c.932+2T>C](/variant/alg13-c-932-plus-2t-c), [ALG13 p.Ala1044Thr](/variant/alg13-p-ala1044thr), [ALG13 p.Ala173Val](/variant/alg13-p-ala173val).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-14); 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 412610). 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.*