Is PRSS1 p.Asp199= (c.597T>C) pathogenic?

PRSS1 p.Asp199= (c.597T>C) is classified Likely benign in PRSS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-25). Common (popmax 35.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hereditary chronic pancreatitis.

What condition is associated with PRSS1 p.Asp199= (c.597T>C)?

PRSS1 p.Asp199= (c.597T>C) is associated with hereditary chronic pancreatitis (ClinVar).

PRSS1 p.Asp199=

Q: How common is PRSS1 p.Asp199= (c.597T>C) in the general population?

PRSS1 p.Asp199= (c.597T>C) is common (popmax 35.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.597T>C · rs1307945104 · VCV1750836

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 35.1%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

hereditary chronic pancreatitis

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.33	GERP -0.11, phastCons 0.99
Overall
CADD	4.627	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 35.1% African / African-American · 20,844/59,350 alleles

Filtering AF 34.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 34.6%

Overall 12.4% 156,141/1,260,754 alleles · common exomes 104,213/1,131,686 · genomes 51,928/129,068 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	38%	3
African / African-Americangrpmax	35.1%	3
Admixed American	33.7%	3
Finnishnot grpmax-eligible	33.1%	3
Ashkenazi Jewishnot grpmax-eligible	23.8%	4
Middle Eastern	15.7%	6
South Asian	14.6%	7
Remaining individualsnot grpmax-eligible	13%	8
European (non-Finnish)	9.07%	11
East Asian	7.03%	14

Amish shows a higher raw frequency than the grpmax group above it. 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.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PRSS1
Protein: p.Asp199=
Coding: c.597T>C
MANE Select: NM_002769
dbSNP: rs1307945104
Type: single nucleotide variant
Location: chr7:142752873 (GRCh38)

Full PRSS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary chronic pancreatitis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant hereditary chronic pancreatitis (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Childhood
Prevalence: 1-9 / 1 000 000 (France)

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/prss1-p-asp199 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown