Is PRSS1 p.Phe18Leu (c.52T>C) pathogenic?

PRSS1 p.Phe18Leu (c.52T>C) is classified Uncertain significance in PRSS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-09-15). AlphaMissense: ambiguous (0.4998); Absent from gnomAD v4.1; Associated with hereditary chronic pancreatitis.

What condition is associated with PRSS1 p.Phe18Leu (c.52T>C)?

PRSS1 p.Phe18Leu (c.52T>C) is associated with hereditary chronic pancreatitis (ClinVar).

How common is PRSS1 p.Phe18Leu (c.52T>C) in the general population?

PRSS1 p.Phe18Leu (c.52T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRSS1 p.Phe18Leu (c.52T>C)?

AlphaMissense predicts ambiguous (score 0.4998) — an in-silico prediction, not a clinical call.

PRSS1 p.Phe18Leu

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

c.52T>C · rs2485731992 · VCV1746698

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4998 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

hereditary chronic pancreatitis

Computational evidence

Protein change
AlphaMissense	0.4998	ambiguous
REVEL	0.179	moderately benign-leaning
SaProt	LLR -5.58	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -6.1	GERP -3.7
Regional constraint	o/e 1.20	unconstrained · MANE · 3,532 bp · p 0.00039 · regional, not allelic
Overall
CADD	0.003	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

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.Phe18Leu
Coding: c.52T>C
MANE Select: NM_002769
dbSNP: rs2485731992
Type: single nucleotide variant
Location: chr7:142750566 (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-phe18leu (accessed [today's date]).

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