Is CPA1 p.Phe379= (c.1137C>T) pathogenic?

CPA1 p.Phe379= (c.1137C>T) is classified Likely benign in CPA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-06). Ultra-rare (popmax 0.0134%, eas); Associated with hereditary chronic pancreatitis.

What condition is associated with CPA1 p.Phe379= (c.1137C>T)?

CPA1 p.Phe379= (c.1137C>T) is associated with hereditary chronic pancreatitis (ClinVar).

How common is CPA1 p.Phe379= (c.1137C>T) in the general population?

CPA1 p.Phe379= (c.1137C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

CPA1 p.Phe379=

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

c.1137C>T · rs570466241 · VCV1115629

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

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 -4.3	GERP -5.1
Overall
CADD	4.889	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,892 alleles

Filtering AF 0.00722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00549%

Overall 0.00217% 35/1,614,182 alleles · ultra-rare exomes 27/1,461,886 · genomes 8/152,296 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,482
African / African-American	0.0133%	7,505
Remaining individualsnot grpmax-eligible	0.008%	12,502
Admixed American	0.005%	20,009
South Asian	0.00439%	22,768
European (non-Finnish)	0.000593%	168,574

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.Phe379=
Coding: c.1137C>T
MANE Select: NM_001868
dbSNP: rs570466241
Type: single nucleotide variant
Location: chr7:130387888 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.41 · 6 PDB
Residue 379: the peptidase m14 domain; a β-strand

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.Phe379Leu Uncertain significance ★★ ⚠ 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
CPA1 p.Ala111Glu Uncertain significance ★★ ⚠ same condition
CPA1 p.Ala120Thr Uncertain significance ★★ ⚠ same condition
CPA1 p.Ala193Ser 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-phe379 (accessed [today's date]).

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