# NM_002769.5(PRSS1):c.612G>A (p.Val204=)

https://sugi.bio/variant/prss1-p-val204

## Summary

**PRSS1 p.Val204= (c.612G>A)** is classified **Likely benign** in PRSS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-11-09). Very rare (popmax 8.47e-05%, nfe); Associated with hereditary chronic pancreatitis.

**At a glance:** Likely benign · review: Multiple submitters · rsID rs868107413 · 2 submitters · 1 linked condition · very rare (popmax 8.47e-05%, nfe)

## For patients & families {#patients}

This is a change in the PRSS1 gene that is classified as likely benign — not considered disease-causing, submitted by 2 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.Val204= |
| Coding change (HGVS c.) | c.612G>A |
| dbSNP | [rs868107413](https://www.ncbi.nlm.nih.gov/snp/rs868107413/) |
| Variant type | single nucleotide variant |
| Location | chr7:142752888-142752888 (GRCh38) |
| ClinVar | [VCV1751780](https://www.ncbi.nlm.nih.gov/clinvar/variation/1751780/) |

**All HGVS expressions:** `LRG_1013:g.8405G>A`, `LRG_1013t1:c.612G>A`, `NC_000007.13:g.142460739G>A`, `NC_000007.14:g.142752888G>A`, `NG_001333.2:g.586556G>A`, `NG_008307.3:g.8405G>A`, `NM_002769.5:c.612G>A`, `NR_172947.1:n.554G>A`, `NR_172948.1:n.551G>A`, `NR_172949.1:n.551G>A`, `NR_172950.1:n.465G>A`, `NR_172951.1:n.399G>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 3.181, GERP 1.85, phastCons 1 — highly conserved position (PP3-type support)
- CADD: **PHRED 3.199**. 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.*
- 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 **8.47e-05%** (nfe) · 1/1,179,978 in the highest group · 1/152,198 alleles overall — very rare (popmax 8.47e-05%, nfe).

*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}

**Likely benign** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2022-11-09.

**Submitter consensus:** unanimous (2/2 Likely benign).

**Submission history:** 2 submissions (2022); classifications have been stable.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Ambry Genetics | Likely benign | criteria provided, single submitter | clinical testing | 2022-08-28 |
| Labcorp Genetics (formerly Invitae), Labcorp | Likely benign | criteria provided, single submitter | clinical testing | 2022-11-09 |

## Associated conditions {#conditions}

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

**Reported phenotype names (ClinVar):** Hereditary pancreatitis, 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 2026-10-06); 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 1751780). 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.*