Is PRSS1 p.Pro17Ser (c.49C>T) pathogenic?

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.

What condition is associated with PRSS1 p.Pro17Ser (c.49C>T)?

PRSS1 p.Pro17Ser (c.49C>T) is associated with hereditary chronic pancreatitis (ClinVar).

What do computational predictors say about PRSS1 p.Pro17Ser (c.49C>T)?

AlphaMissense predicts likely benign (score 0.1161) — an in-silico prediction, not a clinical call.

PRSS1 p.Pro17Ser

Q: How common is PRSS1 p.Pro17Ser (c.49C>T) in the general population?

PRSS1 p.Pro17Ser (c.49C>T) is common (popmax 30.8%, 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.49C>T · rs770782578 · VCV1206231

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1161 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 30.8%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

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
AlphaMissense	0.1161	likely benign
REVEL	0.207	benign-leaning
SaProt	LLR -7.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.27	GERP -1.8, phastCons 0.004
Regional constraint	o/e 1.20	unconstrained · MANE · 3,532 bp · p 0.00039 · regional, not allelic
Overall
CADD	6.149	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 30.8% African / African-American · 10,598/34,360 alleles

Filtering AF 30.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 30.2%

Overall 8.74% 71,579/818,976 alleles · common exomes 49,138/736,944 · genomes 22,441/82,032 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	30.8%	3
Finnishnot grpmax-eligible	25.8%	4
Amishnot grpmax-eligible	24%	4
Admixed American	14.9%	7
Ashkenazi Jewishnot grpmax-eligible	14.1%	7
Middle Eastern	9.7%	10
Remaining individualsnot grpmax-eligible	8.98%	11
European (non-Finnish)	6.99%	14
East Asian	3.44%	29
South Asian	2.85%	35

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.Pro17Ser
Coding: c.49C>T
MANE Select: NM_002769
dbSNP: rs770782578
Type: single nucleotide variant
Location: chr7:142750563 (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-pro17ser (accessed [today's date]).

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