# NM_001807.6(CEL):c.1801G>A (p.Ala601Thr)

https://sugi.bio/variant/cel-p-ala601thr

## Summary

**CEL p.Ala601Thr (c.1801G>A)** is classified **Benign** in CEL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-01). Rare (popmax 0.334%, mid).

**At a glance:** Benign · review: Single submitter · 1 submitter · rare (popmax 0.334%, mid)

## For patients & families {#patients}

This is a change in the CEL gene that is classified as benign — not considered disease-causing, submitted by 1 submitter.

*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 | [CEL](https://sugi.bio/atlas/gene/CEL/) |
| Protein change (HGVS p.) | p.Ala601Thr |
| Coding change (HGVS c.) | c.1801G>A |
| MANE Select transcript | [NM_001807](https://www.ncbi.nlm.nih.gov/nuccore/NM_001807) |
| Variant type | single nucleotide variant |
| Location | chr9:133071303-133071303 (GRCh38) |
| ClinVar | [VCV3771079](https://www.ncbi.nlm.nih.gov/clinvar/variation/3771079/) |

**All HGVS expressions:** `NC_000009.11:g.135946690G>A`, `NC_000009.12:g.133071303G>A`, `NG_016394.1:g.14326G>A`, `NM_001807.6:c.1801G>A`

## 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 0.179, GERP -1.42 — weakly conserved position
- CADD: **PHRED 17.24**. 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 1.11** across the covering region of the MANE Select transcript (133,071,119–133,071,761), spanning 642 bp. Chi-square p 0.096. 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 **0.334%** (mid) · FAF95 0.157% · FAF99 0.14% · 7/2,094 in the highest group · 256/520,104 alleles overall — rare (popmax 0.334%, mid).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| Ashkenazi Jewish (not grpmax-eligible) | 0.533% | 188 |
| Middle Eastern (grpmax) | 0.334% | 299 |
| South Asian | 0.183% | 546 |
| Remaining individuals (not grpmax-eligible) | 0.0607% | 1,648 |
| Admixed American | 0.0426% | 2,347 |
| European (non-Finnish) | 0.0175% | 5,715 |
| African / African-American | 0.00692% | 14,454 |
| East Asian | 0.00304% | 32,928 |

Ashkenazi Jewish 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}

**CEL** population constraint: LOEUF 0.972, pLI 3.4493e-10, missense-Z 1.4207. *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):

- **maturity-onset diabetes of the young type 8** — Moderate (AD)

## Protein context {#protein}

Residue **601** lies in the 'disordered' region; the '17 x 11 aa tandem repeats, glycodomain, o-linked (mucin type)' region.

AlphaFold model confidence (whole protein): pLDDT 84.10, 69% of residues very-high.

**7 experimental structure(s)** (PDB): [1F6W](https://www.rcsb.org/structure/1F6W), [1JMY](https://www.rcsb.org/structure/1JMY), [6H0T](https://www.rcsb.org/structure/6H0T), [6H0V](https://www.rcsb.org/structure/6H0V), [6H18](https://www.rcsb.org/structure/6H18), [6H19](https://www.rcsb.org/structure/6H19).

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

*Describes the biological roles of CEL (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.*


### Pathways affected {#pathways}

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

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Developmental Lineage of Pancreatic Acinar Cells](https://reactome.org/content/detail/R-HSA-9925561) | curated |
| [Digestion of dietary lipid](https://reactome.org/content/detail/R-HSA-192456) | curated |

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

**Biological process:** pancreatic juice secretion, intestinal cholesterol absorption.

## Clinical significance {#significance}

**Benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2025-12-01.

**Submitter consensus:** unanimous (1/1 Benign).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| CeGaT Center for Human Genetics Tuebingen | Benign | criteria provided, single submitter | clinical testing | 2025-12-01 |

**Reported phenotype names (ClinVar):** not provided, none provided.

## Similar variants {#similar}

Related CEL variant pages (same residue, condition, or type): [CEL p.Ala601Pro](/variant/cel-p-ala601pro), [CEL p.Ala601Gly](/variant/cel-p-ala601gly), [CEL p.Ala601Asp](/variant/cel-p-ala601asp), [CEL p.Ala601fs](/variant/cel-p-ala601fs), [CEL c.67-3C>A](/variant/cel-c-67-minus-3c-a), [CEL p.Ala295Ser](/variant/cel-p-ala295ser), [CEL p.Ala548Glu](/variant/cel-p-ala548glu), [CEL p.Ala722Val](/variant/cel-p-ala722val).

### 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 3771079). 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.*