Is CTRC c.40+18G>A pathogenic?

CTRC c.40+18G>A is classified Likely benign in CTRC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-20). Ultra-rare (popmax 0.0164%, mid); Associated with hereditary chronic pancreatitis.

What condition is associated with CTRC c.40+18G>A?

CTRC c.40+18G>A is associated with hereditary chronic pancreatitis (ClinVar).

How common is CTRC c.40+18G>A in the general population?

CTRC c.40+18G>A is ultra-rare (popmax 0.0164%, mid) (gnomAD).

CTRC c.40+18G>A

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

rs1708076823 · VCV994092

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

hereditary chronic pancreatitis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +18	near-intronic (+18 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.31	GERP -2.3
Non-coding constraint	Z 2.88	1 kb window · o/e 0.81 · regional · uncalibrated
Overall
CADD	6.696	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,613,750 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.00133%	74,922
European (non-Finnish)	0.000169%	589,998

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
Coding: c.40+18G>A
MANE Select: NM_007272
dbSNP: rs1708076823
Type: single nucleotide variant
Location: chr1:15438522 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.03 · 1 PDB

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 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
CTRC p.Ala12Val Uncertain significance ★★ ⚠ same condition
CTRC p.Ala184Val 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-c-40-plus-18g-a (accessed [today's date]).

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