Is CTRC p.Arg29Ter (c.85C>T) pathogenic?

CTRC p.Arg29Ter (c.85C>T) is classified Pathogenic/Likely pathogenic in CTRC (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-05-31). Ultra-rare (popmax 0.0182%, mid); Associated with hereditary chronic pancreatitis.

What condition is associated with CTRC p.Arg29Ter (c.85C>T)?

CTRC p.Arg29Ter (c.85C>T) is associated with hereditary chronic pancreatitis (ClinVar).

How common is CTRC p.Arg29Ter (c.85C>T) in the general population?

CTRC p.Arg29Ter (c.85C>T) is ultra-rare (popmax 0.0182%, mid) (gnomAD).

CTRC p.Arg29Ter

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

c.85C>T · rs747905422 · VCV576351

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0182%, mid)

Conditions

hereditary chronic pancreatitis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 8
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.84	GERP -2.5, phastCons 0.99
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0182% Middle Eastern · 1/5,488 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.0023% 37/1,611,576 alleles · ultra-rare exomes 35/1,459,508 · genomes 2/152,068 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0182%	5,488
African / African-American	0.00535%	18,706
South Asian	0.00331%	30,191
European (non-Finnish)	0.00237%	42,124
Remaining individualsnot grpmax-eligible	0.0016%	62,326

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.Arg29Ter
Coding: c.85C>T
MANE Select: NM_007272
dbSNP: rs747905422
Type: single nucleotide variant
Location: chr1:15440344 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.03 · 1 PDB
Residue 29: a UniProt-annotated variant site (found in patients with chronic pancreatitis; uncertain significance)

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.Arg29Gln Uncertain significance ★★ ⚠ same residue
CTRC p.Arg29Leu Uncertain significance ★★ ⚠ same residue
CTRC p.Arg29Pro Uncertain significance ★ ⚠ same residue
CTRC p.Arg29= Likely benign ★ same residue
CTRC c.494-1G>C 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

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-arg29ter (accessed [today's date]).

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