Is PRSS1 p.Val214= (c.642C>A) pathogenic?

PRSS1 p.Val214= (c.642C>A) is classified Likely benign in PRSS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-22). Ultra-rare (popmax 0.0506%, afr); Associated with hereditary chronic pancreatitis.

What condition is associated with PRSS1 p.Val214= (c.642C>A)?

PRSS1 p.Val214= (c.642C>A) is associated with hereditary chronic pancreatitis (ClinVar).

How common is PRSS1 p.Val214= (c.642C>A) in the general population?

PRSS1 p.Val214= (c.642C>A) is ultra-rare (popmax 0.0506%, afr) (gnomAD).

PRSS1 p.Val214=

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

c.642C>A · rs141697925 · VCV1140241

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0506%, afr)

Conditions

hereditary chronic pancreatitis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.3	GERP -2.7
Overall
CADD	1.268	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0506% African / African-American · 38/75,028 alleles

Filtering AF 0.0379% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0334%

Overall 0.00347% 56/1,614,130 alleles · ultra-rare exomes 33/1,461,840 · genomes 23/152,290 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0506%	1,974
Remaining individualsnot grpmax-eligible	0.016%	6,250
Admixed American	0.0133%	7,502

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.Val214=
Coding: c.642C>A
MANE Select: NM_002769
dbSNP: rs141697925
Type: single nucleotide variant
Location: chr7:142752918 (GRCh38)
Gene constraint: LOEUF 1.301 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 92.24 · 12 PDB
Residue 214: the peptidase s1 domain; a β-strand

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)

Similar variants

PRSS1 p.Val214Ile Uncertain significance ★ ⚠ same residue
PRSS1 p.Val214Leu Uncertain significance ★ ⚠ same residue
PRSS1 p.Ala16Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
PRSS1 p.Arg116Cys Pathogenic/Likely pathogenic ★★ same condition
PRSS1 p.Arg122Cys Pathogenic ★★ same condition
PRSS1 p.Arg122His Pathogenic/Likely pathogenic ★★ ⚠ same condition
PRSS1 p.Asn29Ile Pathogenic ★★ ⚠ same condition
PRSS1 c.200+1G>C Uncertain significance ★★ same condition

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-val214 (accessed [today's date]).

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