Is CPA1 p.Asp115= (c.345C>T) pathogenic?

CPA1 p.Asp115= (c.345C>T) is classified Likely benign in CPA1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-06). Very rare (popmax 8.47e-05%, nfe); Associated with hereditary chronic pancreatitis.

What condition is associated with CPA1 p.Asp115= (c.345C>T)?

CPA1 p.Asp115= (c.345C>T) is associated with hereditary chronic pancreatitis (ClinVar).

How common is CPA1 p.Asp115= (c.345C>T) in the general population?

CPA1 p.Asp115= (c.345C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

CPA1 p.Asp115=

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

c.345C>T · rs2117500618 · VCV1562403

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 -0.31	GERP -5
Overall
CADD	2.076	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,024 alleles

Overall 0.000137% 2/1,461,746 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,500
European (non-Finnish)grpmax	8.47e-05%	1,180,025

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CPA1
Protein: p.Asp115=
Coding: c.345C>T
MANE Select: NM_001868
dbSNP: rs2117500618
Type: single nucleotide variant
Location: chr7:130381827 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.41 · 6 PDB
Residue 115: a turn

Full CPA1 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

CPA1 p.Asp115His Uncertain significance ★★ ⚠ same residue
CPA1 p.Asp115Gly Uncertain significance ★ ⚠ same residue
CPA1 p.Asp115Val Uncertain significance ★ ⚠ same residue
CPA1 p.Asp115Asn Likely benign ★ ⚠ same residue
CPA1 c.1072+1G>T Uncertain significance ★★ same condition
CPA1 c.147+4A>C Uncertain significance ★★ same condition
CPA1 c.586-2A>G Uncertain significance ★★ same condition
CPA1 c.696+5C>T 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/cpa1-p-asp115 (accessed [today's date]).

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