Is PRSS1 p.Phe47Val (c.139T>G) pathogenic?

PRSS1 p.Phe47Val (c.139T>G) is classified Uncertain significance in PRSS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-27). AlphaMissense: likely pathogenic (0.6135); Very rare (popmax 8.48e-05%, nfe); Associated with hereditary chronic pancreatitis.

What condition is associated with PRSS1 p.Phe47Val (c.139T>G)?

PRSS1 p.Phe47Val (c.139T>G) is associated with hereditary chronic pancreatitis (ClinVar).

How common is PRSS1 p.Phe47Val (c.139T>G) in the general population?

PRSS1 p.Phe47Val (c.139T>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about PRSS1 p.Phe47Val (c.139T>G)?

AlphaMissense predicts likely pathogenic (score 0.6135) — an in-silico prediction, not a clinical call.

PRSS1 p.Phe47Val

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

c.139T>G · rs2485733543 · VCV1771747

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6135 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

3/3 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	0.6135	likely pathogenic
REVEL	0.709	pathogenic-leaning
SaProt	LLR -12.23	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.37	GERP 0.68, phastCons 0.97
Regional constraint	o/e 1.20	unconstrained · MANE · 3,532 bp · p 0.00039 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,872 alleles

Overall 6.2e-05% 1/1,614,034 alleles · very rare exomes 1/1,461,666 · genomes 0/152,368 · joint denominator

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.Phe47Val
Coding: c.139T>G
MANE Select: NM_002769
dbSNP: rs2485733543
Type: single nucleotide variant
Location: chr7:142750653 (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-phe47val (accessed [today's date]).

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