Is PRSS1 p.Ala221= (c.663C>T) pathogenic?

PRSS1 p.Ala221= (c.663C>T) is classified Likely benign in PRSS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-29). Absent from gnomAD v4.1; Associated with hereditary chronic pancreatitis.

What condition is associated with PRSS1 p.Ala221= (c.663C>T)?

PRSS1 p.Ala221= (c.663C>T) is associated with hereditary chronic pancreatitis (ClinVar).

How common is PRSS1 p.Ala221= (c.663C>T) in the general population?

PRSS1 p.Ala221= (c.663C>T) is absent from gnomAD v4.1 (gnomAD).

PRSS1 p.Ala221=

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

c.663C>T · rs1180557624 · VCV3222824

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary chronic pancreatitis

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 -4	GERP -3.7
Overall
CADD	8.513	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRSS1
Protein: p.Ala221=
Coding: c.663C>T
dbSNP: rs1180557624
Type: single nucleotide variant
Location: chr7:142752939 (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-ala221 (accessed [today's date]).

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