# NM_002769.5(PRSS1):c.49C>T (p.Pro17Ser)

https://sugi.bio/variant/prss1-p-pro17ser

## Summary

**PRSS1 p.Pro17Ser (c.49C>T)** is classified **Benign/Likely benign** in PRSS1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2021-02-25). AlphaMissense: likely benign (0.1161); Common (popmax 30.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hereditary chronic pancreatitis.

**At a glance:** Benign/Likely benign · review: Multiple submitters · rsID rs770782578 · 4 submitters · 1 linked condition · AlphaMissense likely benign · common (popmax 30.8%, afr) — too common for a highly-penetrant pathogenic allele

> **Built without this gene's context.** ClinVar files this variant under an overlapping gene, so its own gene's record set does not contain it and this page is assembled from the variant alone. Gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up — absent from this page, not from the data.

## For patients & families {#patients}

This is a change in the PRSS1 gene that is classified as benign/likely benign — not considered disease-causing, submitted by 4 submitters, and is linked to hereditary chronic pancreatitis.

*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, Childhood |
| Prevalence | 1-9 / 1 000 000 (France) |
| Clinical trials | 8 registered for this condition — see ClinicalTrials.gov |

**Commonly reported features of Autosomal dominant hereditary chronic pancreatitis** (across patients with this condition; presentation varies — frequencies from Orphanet):

- Leukocytosis — Very frequent (99-80%)
- Abdominal pain — Very frequent (99-80%)
- Elevated circulating C-reactive protein concentration — Very frequent (99-80%)
- Recurrent pancreatitis — Very frequent (99-80%)
- Abnormal enzyme/coenzyme activity — Frequent (79-30%)
- Diabetes mellitus — Occasional (29-5%)
- Jaundice — Occasional (29-5%)
- Pancreatic calcification — Occasional (29-5%)

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0006632/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [PRSS1](https://sugi.bio/atlas/gene/PRSS1/) |
| Protein change (HGVS p.) | p.Pro17Ser |
| Coding change (HGVS c.) | c.49C>T |
| MANE Select transcript | [NM_002769](https://www.ncbi.nlm.nih.gov/nuccore/NM_002769) |
| dbSNP | [rs770782578](https://www.ncbi.nlm.nih.gov/snp/rs770782578/) |
| Variant type | single nucleotide variant |
| Location | chr7:142750563-142750563 (GRCh38) |
| ClinVar | [VCV1206231](https://www.ncbi.nlm.nih.gov/clinvar/variation/1206231/) |

**All HGVS expressions:** `LRG_1013:g.6080C>T`, `LRG_1013t1:c.49C>T`, `NC_000007.13:g.142458414C>T`, `NC_000007.14:g.142750563C>T`, `NG_001333.2:g.584231C>T`, `NG_008307.3:g.6080C>T`, `NM_002769.5:c.49C>T`

## Computational & population evidence {#evidence}

**Concordance:** Evidence sources **disagree** — common (popmax 30.8%, afr) — too common for a highly-penetrant pathogenic allele.

- AlphaMissense **likely benign** (0.1161)
- REVEL 0.207 (benign-leaning) — agrees with AlphaMissense
- SaProt LLR -7.449 (tolerated) — agrees with AlphaMissense
- → **In-silico consensus:** AlphaMissense, REVEL and SaProt all call this tolerated
- Conservation: phyloP 0.27, GERP -1.79, phastCons 0.004 — weakly conserved position
- CADD: **PHRED 6.149**. 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 1.20** across the covering region of the MANE Select transcript (142,749,485–142,753,017), spanning 3,532 bp. Chi-square p 0.00039. Describes the region, not this allele; gnomAD v4.1.1's own constrained determination. *Descriptive; no ACMG code applied.*
- SpliceAI: **not looked up on this page** — it was served without the gene's SpliceAI index, so no lookup was made. This is a gap in this page, not in the data, and says nothing about whether a splicing effect is predicted.
- Population frequency (gnomAD v4.1): grpmax **30.8%** (afr) · FAF95 30.4% · FAF99 30.2% · 10,598/34,360 in the highest group · 71,579/818,976 alleles overall — common (popmax 30.8%, afr) — too common for a highly-penetrant pathogenic allele.

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| African / African-American (grpmax) | 30.8% | 3 |
| Finnish (not grpmax-eligible) | 25.8% | 4 |
| Amish (not grpmax-eligible) | 24% | 4 |
| Admixed American | 14.9% | 7 |
| Ashkenazi Jewish (not grpmax-eligible) | 14.1% | 7 |
| Middle Eastern | 9.7% | 10 |
| Remaining individuals (not grpmax-eligible) | 8.98% | 11 |
| European (non-Finnish) | 6.99% | 14 |
| East Asian | 3.44% | 29 |
| South Asian | 2.85% | 35 |

*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.*

## Clinical significance {#significance}

**Benign/Likely benign** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2021-02-25.

**Submitter consensus:** conflicting (2 Likely benign, 2 Benign).

**Submission history:** 2 submissions (2020–2021); classifications have differed over time.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | Likely benign | no assertion criteria provided | clinical testing |  |
| Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Benign | no assertion criteria provided | clinical testing |  |
| Sema4, Sema4 | Likely benign | criteria provided, single submitter | curation | 2021-02-25 |
| Ambry Genetics | Benign | criteria provided, single submitter | clinical testing | 2020-04-21 |

## Associated conditions {#conditions}

[hereditary chronic pancreatitis](https://sugi.bio/atlas/disease/hereditary-chronic-pancreatitis/).

**Reported phenotype names (ClinVar):** Hereditary pancreatitis, not provided, not specified, none provided, AllHighlyPenetrant, Hereditary chronic pancreatitis, PRSS1-Related Hereditary Pancreatitis.

### 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 1206231). 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.*