Is CTRC p.Pro249= (c.747G>A) pathogenic?

CTRC p.Pro249= (c.747G>A) is classified Benign/Likely benign in CTRC (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-10). Rare (popmax 0.345%, mid); Associated with hereditary chronic pancreatitis.

What condition is associated with CTRC p.Pro249= (c.747G>A)?

CTRC p.Pro249= (c.747G>A) is associated with hereditary chronic pancreatitis (ClinVar).

How common is CTRC p.Pro249= (c.747G>A) in the general population?

CTRC p.Pro249= (c.747G>A) is rare (popmax 0.345%, mid) (gnomAD).

CTRC p.Pro249=

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

c.747G>A · rs150078209 · VCV416442

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.345%, mid)

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	GERP -5.2
Overall
CADD	1.977	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.345% Middle Eastern · 21/6,084 alleles

Filtering AF 0.231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.194%

Overall 0.011% 177/1,613,818 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.345%	290
East Asian	0.049%	2,041
African / African-American	0.0187%	5,351
Remaining individualsnot grpmax-eligible	0.0096%	10,413
South Asian	0.00878%	11,386
European (non-Finnish)	0.00865%	11,567
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600
Admixed American	0.00333%	30,002
Finnishnot grpmax-eligible	0.00156%	64,014

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: CTRC
Protein: p.Pro249=
Coding: c.747G>A
MANE Select: NM_007272
dbSNP: rs150078209
Type: single nucleotide variant
Location: chr1:15445704 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.03 · 1 PDB
Residue 249: the peptidase s1 domain; a UniProt-annotated variant site (in pctt; results in reduced protein secretion and loss of activity)

Full CTRC 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

CTRC p.Pro249Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
CTRC p.Pro249Ser Uncertain significance ★ ⚠ same residue
CTRC c.494-1G>C Pathogenic/Likely pathogenic ★★ same condition
CTRC p.Arg29Ter Pathogenic/Likely pathogenic ★★ same condition
CTRC p.Gln174Ter Pathogenic/Likely pathogenic ★★ same condition
CTRC c.356+1G>A Uncertain significance ★★ same condition
CTRC c.40+4A>G Uncertain significance ★★ same condition
CTRC c.40+6C>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/ctrc-p-pro249 (accessed [today's date]).

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