Is CTRC p.Arg241= (c.721C>A) pathogenic?

CTRC p.Arg241= (c.721C>A) is classified Likely benign in CTRC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-17). Very rare (popmax 0.00333%, amr); Associated with hereditary chronic pancreatitis.

What condition is associated with CTRC p.Arg241= (c.721C>A)?

CTRC p.Arg241= (c.721C>A) is associated with hereditary chronic pancreatitis (ClinVar).

How common is CTRC p.Arg241= (c.721C>A) in the general population?

CTRC p.Arg241= (c.721C>A) is very rare (popmax 0.00333%, amr) (gnomAD).

CTRC p.Arg241=

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

c.721C>A · rs771229796 · VCV1757754

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

hereditary chronic pancreatitis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -7.2	GERP -5.2
Overall
CADD	0.461	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,016 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,614,180 alleles · very rare exomes 2/1,461,880 · genomes 0/152,300 · joint denominator

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.Arg241=
Coding: c.721C>A
MANE Select: NM_007272
dbSNP: rs771229796
Type: single nucleotide variant
Location: chr1:15445678 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.03 · 1 PDB
Residue 241: the peptidase s1 domain

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.Arg241Trp Uncertain significance ★★ ⚠ same residue
CTRC p.Arg241Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
CTRC p.Arg241Gly Uncertain significance ★ ⚠ same residue
CTRC p.Arg241Leu Likely benign ★ 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

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-arg241 (accessed [today's date]).

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